Catatonia

Psychiatric MONDO:0800105 Pathograph 26 Show in embeddings browser Mental Health Disorder Psychomotor Disorder

Catatonia is a transdiagnostic psychomotor syndrome affecting movement, speech, affect and behavior. It occurs with psychiatric, neurological, neurodevelopmental and general medical conditions. Hypokinetic, hyperkinetic and qualitatively abnormal motor signs can overlap or fluctuate within an episode. Malignant catatonia includes clinically significant autonomic dysfunction and can be life-threatening. Imaging and pharmacological observations implicate interacting GABAergic, glutamatergic, dopaminergic and distributed network disturbances, but no single mechanism or diagnostic biomarker accounts for all presentations. Benzodiazepines and electroconvulsive therapy are first-line treatments; treatment of the underlying condition and prevention of medical complications are also required.

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11
Pathophys.
25
Phenotypes
4
Hypotheses
5
Gaps
26
Pathograph
1
Genes
20
Medical Actions
12
Differentials
7
Trials
4
References
🏷

Classifications

Harrison's Part
NEUROLOGIC
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Mechanistic Hypotheses

4
Distributed psychomotor network model
distributed_psychomotor_network_model CANONICAL
Evidence balance 2 support
A leading integrative model proposes that heterogeneous upstream conditions disturb interacting psychomotor networks. Imaging associations provide candidate circuit locations, but the evidence is enriched for schizophrenia-spectrum cohorts and postacute states. Its designation as the organizing model does not establish a common causal pathway or a validated biomarker across etiologies.
Pathograph links
Cortical GABA-A Receptor-Mediated Inhibition Deficit -> Distributed Psychomotor Network Destabilization INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Reduced Striatal Dopaminergic Transmission -> Distributed Psychomotor Network Destabilization INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Autoimmune NMDA Receptor Perturbation -> Distributed Psychomotor Network Destabilization INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Orbitofrontal Emotional-Motor Processing Dysfunction -> Distributed Psychomotor Network Destabilization INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Distributed Psychomotor Network Destabilization -> Hypokinetic Psychomotor Output INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Distributed Psychomotor Network Destabilization -> Hyperkinetic Psychomotor Output INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Distributed Psychomotor Network Destabilization -> Autonomic Decompensation INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Show evidence (2 references)
PMID:42431537 SUPPORT Human Clinical
"The best-supported mechanistic model to date comes from neuroimaging studies implicating cortico-striatal-thalamic, cortico-cerebellar, orbitofrontal, cingulate, and motor-premotor networks."
States the network membership of the canonical model and its evidential basis in neuroimaging.
PMID:42431537 SUPPORT Human Clinical
"the evidence supports a convergent model in which diverse upstream liabilities destabilize shared psychomotor networks, producing a recognizable but heterogeneous syndrome"
The convergence claim that justifies modeling catatonia as one entity with many entry points rather than as many disease-specific mechanisms.
Reduced cortical GABA-A-mediated inhibition in akinetic catatonia
gabaergic_deficit_model ALTERNATIVE
Evidence balance 2 support
Benzodiazepine responses and reduced iomazenil binding motivate a GABAergic hypothesis. The small receptor-imaging study identifies altered ligand binding, not a demonstrated receptor lesion or direct measurement of inhibitory transmission. GABAergic mechanisms may interact with other signaling systems and need not explain every clinical presentation.
Pathograph links
Cortical GABA-A Receptor-Mediated Inhibition Deficit -> Distributed Psychomotor Network Destabilization INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Show evidence (2 references)
PMID:10486389 SUPPORT INDIRECT PRIMARY RESULT Human Clinical
"Reduced iomazenil binding suggests decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia."
The authors interpret reduced ligand binding as suggesting lower receptor density; causality and functional impairment are not established.
PMID:42431537 SUPPORT Human Clinical
"Neurochemical evidence supports the notion of interacting disturbances in GABAergic inhibition, glutamatergic/NMDA-mediated excitation, and dopaminergic modulation rather than a single-transmitter explanation."
Qualifies the GABA-only account: the contemporary synthesis treats GABAergic inhibition as one interacting term, not the whole mechanism.
Reduced striatal dopaminergic transmission as a transdiagnostic psychomotor substrate
striatal_dopamine_hypofunction_model ALTERNATIVE
Evidence balance 3 support
Reduced striatal dopamine signaling is proposed as one contributor to the hypokinetic presentation. Catatonia-specific imaging evidence is sparse, and evidence from Parkinson disease cannot establish an identical mechanism. The review includes single catatonic subjects within PET studies and a small longitudinal DAT-SPECT series. CSF homovanillic acid findings are inconsistent, including elevation in catatonia; these measurements lack regional and temporal specificity. Dopaminergic treatment reports remain preliminary, and the hypothesis does not explain all excited or alternating presentations.
Pathograph links
Reduced Striatal Dopaminergic Transmission -> Distributed Psychomotor Network Destabilization INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Show evidence (3 references)
PMID:40966690 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Evidence for drug-induced parkinsonism, neuroleptic malignant syndrome, catatonia, obsessional slowness and hyperkinetic disorders is less comprehensive and requires further research."
The review explicitly limits the imaging evidence for catatonia.
PMID:40966690 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In catatonia, one study found increased HVA levels relative to healthy controls."
A conflicting biochemical finding prevents treating low CSF dopamine metabolites as an established general feature.
PMID:40966690 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"However, the evidence in catatonia and depression remains preliminary with small sample sizes and a lack of well-conducted clinical trials."
Qualifies pharmacological support for the proposed mechanism.
Immune-mediated NMDA receptor perturbation in autoimmune subgroups
immune_mediated_model EMERGING
Evidence balance 2 support
In a mechanistically distinct subgroup, catatonia arises from autoimmune perturbation of glutamatergic signaling — most clearly in NMDA receptor antibody encephalitis, where catatonia is present in a majority of reported cases. The subgroup matters clinically because its treatment is immunotherapy directed at the antibody-mediated process, not only benzodiazepines. The arm is EMERGING rather than established as a general mechanism because it accounts for a subgroup rather than the syndrome, and because peripheral inflammatory biomarkers remain nonspecific.
Pathograph links
Autoimmune NMDA Receptor Perturbation -> Distributed Psychomotor Network Destabilization INDIRECT UNKNOWN INTERMEDIATES Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia.
Show evidence (2 references)
PMID:42431537 SUPPORT Human Clinical
"Immune mechanisms are particularly relevant in subgroups, especially in autoimmune encephalitis and inflammatory CNS conditions, whereas peripheral biomarkers remain nonspecific."
Scopes the immune arm to subgroups and records the biomarker limitation that keeps it from generalizing.
PMID:32070914 SUPPORT Human Clinical
"Catatonia was present in 60% of these cases."
Quantifies how strongly catatonia tracks with NMDA receptor antibody encephalitis in the published case literature.
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Discussions and Knowledge Gaps

5
Is there a single mechanism or biomarker that accounts for catatonia across its psychiatric, neurologic, autoimmune, and medical contexts, or is the convergent-network account the correct final level of explanation?
KNOWLEDGE GAP OPEN catatonia_no_unified_mechanism
Attached to
pathophysiology#Distributed Psychomotor Network Destabilization
Catatonia occurs across heterogeneous etiologies, and the available imaging and pharmacological observations do not establish a single causal mechanism. The distributed-network model is an integrative hypothesis. Studies across causes and acute clinical states are needed to test shared network changes and determine whether useful biomarkers are syndrome-wide or restricted to particular etiologies.
Proposed experiments
Prospective acute-state multimodal phenotyping across upstream causes
exp_catatonia_acute_state_multimodal_cohort
Recruit an acute-state catatonia cohort stratified by upstream cause (mood disorder, schizophrenia-spectrum, autoimmune encephalitis, medical or drug-induced) and acquire the same multimodal battery in every stratum: resting-state and emotional-task fMRI, GABA-A receptor imaging, striatal dopaminergic imaging, CSF and serum neuronal autoantibodies, and dimensional Bush-Francis and Northoff scale scoring. The discriminating test is whether the network signature is shared across strata while the neurochemical signature differs by stratum — the prediction of the convergent model — or whether each stratum has its own network signature.
Show evidence (2 references)
PMID:42431537 SUPPORT Human Clinical
"No single biomarker or unified mechanism fully accounts for catatonia across contexts."
The explicit statement of the gap this discussion records.
PMID:42431537 SUPPORT Human Clinical
"Future progress will depend on dimensional phenotyping, multimodal biomarker integration, and subtype-sensitive treatment research."
The authors' own statement of what would close the gap, which the proposed experiment operationalizes.
How much of the imaging evidence for the distributed-network model is an artifact of studying schizophrenia-spectrum patients in the post-acute state rather than catatonia in the acute state across its full diagnostic range?
KNOWLEDGE GAP OPEN catatonia_sampling_and_acute_state_bias
Attached to
pathophysiology#Distributed Psychomotor Network Destabilization pathophysiology#Orbitofrontal Emotional-Motor Processing Dysfunction
Schizophrenia-spectrum and postacute samples dominate the cited imaging studies. Persistent orbitofrontal changes could reflect predisposition, illness consequences or treatment; the study design does not establish which. Generalization to acute catatonia across etiologies requires prospective comparison.
Show evidence (2 references)
PMID:42431537 SUPPORT Human Clinical
"key limitations remain, including the overrepresentation of schizophrenia-spectrum samples and limited acute-state data"
Names both sampling limitations directly.
PMID:15279056 SUPPORT Human Clinical
"Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome"
A worked instance of the acute-state limitation, stated by the original authors.
Can adequately controlled and reported trials improve the predominantly observational treatment evidence for catatonia?
KNOWLEDGE GAP OPEN catatonia_evidence_quality_ceiling
Attached to
pathophysiology#Distributed Psychomotor Network Destabilization
The BAP guideline identifies several randomized trials but describes small samples, high risk of bias, incomplete reporting and restricted populations. The quoted lorazepam response proportion comes from an open prospective study, not a controlled treatment effect. A small number of trials should not be described as an absence of randomized research.
Show evidence (2 references)
PMID:37039129 SUPPORT Human Clinical
"Clinical trials were uncommon, and the recommendations in this guideline are mainly informed by small observational studies, case series and case reports, which highlights the need for randomised controlled trials and prospective cohort studies in this area."
The guideline's own statement of the evidence ceiling.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Several RCTs have been conducted, but they have usually been at high risk of bias, inadequately reported, using outdated treatments or applicable to only a small subset of patients with catatonia"
Distinguishes a limited trial literature from no randomized evidence.
Does neuroleptic malignant syndrome represent a medication-triggered form of malignant catatonia, or do the overlapping clinical syndromes have distinguishable mechanisms?
CONTROVERSY OPEN catatonia_malignant_vs_nms
Attached to
pathophysiology#Autonomic Decompensation pathophysiology#Reduced Striatal Dopaminergic Transmission
The syndromes overlap in rigidity, hyperthermia, altered mental state and autonomic dysfunction. Dopamine-blocker exposure supports NMS, whereas malignant catatonia can arise without it. Some experts consider NMS a form of malignant catatonia; the shared-dopamine model remains a hypothesis rather than an established mechanistic discriminator.
Show evidence (3 references)
PMID:40966690 SUPPORT Human Clinical
"In addition, there are close epidemiological relationships between depression and Parkinson's disease, and between catatonia and neuroleptic malignant syndrome."
Records the epidemiological relationship that a shared-substrate account would explain.
PMID:35861966 SUPPORT Human Clinical
"Malignant catatonia describes catatonia that presents with clinically significant autonomic abnormalities including change in temperature, blood pressure, heart rate, and respiratory rate."
Supplies the definition of the entity on the catatonia side of the controversy.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"many experts consider neuroleptic malignant syndrome (NMS) to be a type of malignant catatonia that is precipitated by dopamine receptor blocking agents."
The resource document describes the exposure relationship and diagnostic overlap.
How should unbound catatonic signs be represented until specific HPO concepts are available?
CURATION TODO OPEN catatonia_hpo_term_gap
Attached to
pathophysiology#Hypokinetic Psychomotor Output
OLS4 HP searches on 2026-10-04 for catatonia, catalepsy and waxy flexibility returned no hits. Stupor returned coma and akinetic mutism, which are not equivalent; mannerism returned motor stereotypy and broader behavior terms. Echopraxia (HP:0020124) and Pressure ulcer (HP:0012399) have specific matching terms and are included. Query pattern: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=catatonia; substitute each listed phrase, URL-encoding spaces. Unbound descriptors retain clinically important signs without false equivalences.
Upstream ontology gap, not a dismech bug. Recorded here so the decision is auditable rather than rediscovered.
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Pathophysiology

11
Cortical GABA-A Receptor-Mediated Inhibition Deficit
Mechanism confidence: Provisional
Reduced cortical GABA-A-mediated inhibition is a hypothesis motivated by benzodiazepine responses and reduced iomazenil binding in a small study of akinetic catatonia. Receptor-ligand binding is a proxy for receptor availability, not a direct measure of inhibitory synaptic transmission. Matching psychiatric controls for diagnosis and medication strengthens the comparison but does not eliminate residual confounding or establish causality.
Distributed psychomotor network model Reduced cortical GABA-A-mediated inhibition in akinetic catatonia
gamma-aminobutyric acid signaling pathway GO:0007214 ↓ DECREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased gamma-aminobutyric acid signaling pathway (GO:0007214). GO:0007214 is a biological process from the Gene Ontology.
sensorimotor cortex Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in sensorimotor cortex.
Downstream
Distributed Psychomotor Network Destabilization Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia. Reduced cortical GABA-A-mediated inhibition in akinetic catatonia Distributed psychomotor network model
Show evidence (2 references)
PMID:10486389 SUPPORT INDIRECT PRIMARY RESULT Human Clinical
"Catatonic patients showed significantly lower iomazenil binding and altered right-left relations in the left sensorimotor cortex compared with psychiatric (p<0.001) and healthy (p<0.001) controls."
A regional binding difference supports the GABAergic hypothesis indirectly; it does not directly measure receptor function or exclude all confounding.
PMID:10486389 SUPPORT INDIRECT BACKGROUND Human Clinical
"Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety which both respond almost immediately to benzodiazepines such as lorazepam."
The introduction restates a clinical response that motivated the study; it is not a receptor-restoration experiment.
Reduced Regional Cortical Perfusion
Mechanism confidence: Provisional
Reduced right lower prefrontal and parietal perfusion was observed in the small akinetic-catatonia SPECT study. This regional blood-flow finding is distinct from reduced iomazenil binding and does not by itself establish GABA-A receptor dysfunction.
Show evidence (1 reference)
PMID:10486389 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal cortex in catatonia"
A separate perfusion measurement; its causal relationship to the syndrome remains uncertain.
Reduced Striatal Dopaminergic Transmission
Mechanism confidence: Provisional
Reduced striatal dopamine signaling is a proposed contributor to hypokinetic catatonia. Human imaging observations are sparse and measure presynaptic synthesis, storage or transporter availability rather than the complete signaling pathway. The direct/indirect basal-ganglia pathway model is mechanistic background; its full sequence has not been demonstrated in catatonia. Pharmacological reports and overlap with neuroleptic malignant syndrome support investigation but are not a universal explanation.
Distributed psychomotor network model Reduced striatal dopaminergic transmission as a transdiagnostic psychomotor substrate
dopaminergic neuron CL:0000700 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves dopaminergic neuron (CL:0000700). CL:0000700 is a cell type from the Cell Ontology. medium spiny neuron CL:1001474 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves medium spiny neuron (CL:1001474). CL:1001474 is a cell type from the Cell Ontology.
dopamine receptor signaling pathway GO:0007212 ↓ DECREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased dopamine receptor signaling pathway, annotated with G protein-coupled dopamine receptor signaling pathway (GO:0007212). GO:0007212 is a biological process from the Gene Ontology.
striatum UBERON:0002435 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in striatum (UBERON:0002435). UBERON:0002435 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Distributed Psychomotor Network Destabilization Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia. Reduced striatal dopaminergic transmission as a transdiagnostic psychomotor substrate Distributed psychomotor network model
Show evidence (3 references)
PMID:40966690 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"Three 18F-FDOPA-PET studies of individuals with psychosis have each included a single patient with catatonia"
The review describes the very small catatonia-specific PET evidence base.
PMID:40966690 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"five older women with catatonia and depression underwent a DAT-SPECT"
The longitudinal transporter-imaging signal comes from a small selected series.
PMID:40966690 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"However, the evidence in catatonia and depression remains preliminary with small sample sizes and a lack of well-conducted clinical trials."
The clinical pharmacological evidence is preliminary.
Autoimmune NMDA Receptor Perturbation
Mechanism confidence: Provisional
Autoimmune NMDA receptor dysfunction provides one etiological route to catatonia in anti-NMDA receptor encephalitis. The downstream circuit sequence generating catatonic signs remains uncertain. Published case reports document both hypokinetic and excited signs, sometimes in the same patient. This subgroup does not establish microglial activation or a general NMDA signaling abnormality in every form of catatonia.
Distributed psychomotor network model Immune-mediated NMDA receptor perturbation in autoimmune subgroups
glutamate receptor signaling pathway GO:0007215 ⚠ ABNORMAL Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal glutamate receptor signaling pathway (GO:0007215). GO:0007215 is a biological process from the Gene Ontology.
Downstream
Distributed Psychomotor Network Destabilization Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia. Immune-mediated NMDA receptor perturbation in autoimmune subgroups Distributed psychomotor network model
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"there is a strong association between anti-NMDA receptor encephalitis and catatonia"
Supports the autoimmune etiological subgroup without asserting a measured cell-specific signaling change.
PMID:42431537 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"Immune mechanisms are particularly relevant in subgroups, especially in autoimmune encephalitis and inflammatory CNS conditions, whereas peripheral biomarkers remain nonspecific."
Scopes the immune model to selected contexts.
PMID:32070914 SUPPORT INDIRECT PRIMARY RESULT Human Clinical
"Immobility/stupor and excitement co-occurred in the same patient in 33% of cases."
A systematic review of selected reports documents overlapping signs; it does not identify a molecular pathway.
Orbitofrontal Emotional-Motor Processing Dysfunction
Mechanism confidence: Provisional
A small emotional-task fMRI study of postacute akinetic catatonia found altered orbitofrontal activation and functional connectivity with premotor cortex. Behavioral and affective symptom scores correlated with orbitofrontal activity, while motor symptoms were related to medial prefrontal activity. A persistent trait abnormality is one interpretation, but postacute sampling cannot distinguish predisposition from consequences of illness or treatment.
Distributed psychomotor network model
orbitofrontal cortex UBERON:0004167 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in orbitofrontal cortex (UBERON:0004167). UBERON:0004167 is an anatomical location from the Uberon multi-species anatomy ontology. prefrontal cortex UBERON:0000451 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in prefrontal cortex (UBERON:0000451). UBERON:0000451 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Distributed Psychomotor Network Destabilization Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia. Distributed psychomotor network model
Show evidence (3 references)
PMID:15279056 SUPPORT INDIRECT PRIMARY RESULT Human Clinical
"Catatonic patients showed alterations in the orbitofrontal cortical activation pattern and in functional connectivity to the premotor cortex in negative and positive emotions compared to psychiatric and healthy controls."
Associational functional imaging localizes a candidate circuit disturbance; it does not demonstrate a causal emotional-motor lesion.
PMID:15279056 SUPPORT INDIRECT PRIMARY RESULT Human Clinical
"Catatonic behavioral and affective symptoms correlated significantly with orbitofrontal activity, whereas catatonic motor symptoms were rather related to medial prefrontal activity."
Dissociates the affective and motor components onto different prefrontal subregions.
PMID:15279056 SUPPORT INDIRECT PRIMARY RESULT Human Clinical
"Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome"
The authors' own caveat: post-acute sampling means this may index predisposition rather than the acute mechanism.
Distributed Psychomotor Network Destabilization
Mechanism confidence: Provisional
A distributed-network model integrates structural and functional imaging associations across cortico-striatal-thalamic, cortico-cerebellar, orbitofrontal, cingulate and motor-premotor regions. Multimodal MRI in schizophrenia-spectrum participants identifies candidate circuits, but does not establish a shared causal substrate across every etiology or catatonic presentation. Most neurochemical-to-network links remain mechanistic hypotheses.
Distributed psychomotor network model
prefrontal cortex UBERON:0000451 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in prefrontal cortex (UBERON:0000451). UBERON:0000451 is an anatomical location from the Uberon multi-species anatomy ontology. striatum UBERON:0002435 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in striatum (UBERON:0002435). UBERON:0002435 is an anatomical location from the Uberon multi-species anatomy ontology. thalamus UBERON:0001897 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in thalamus, annotated with dorsal plus ventral thalamus (UBERON:0001897). UBERON:0001897 is an anatomical location from the Uberon multi-species anatomy ontology. cerebellum UBERON:0002037 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in cerebellum (UBERON:0002037). UBERON:0002037 is an anatomical location from the Uberon multi-species anatomy ontology. primary motor cortex UBERON:0001384 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in primary motor cortex (UBERON:0001384). UBERON:0001384 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Hypokinetic Psychomotor Output Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia. Distributed psychomotor network model
Hyperkinetic Psychomotor Output Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia. Distributed psychomotor network model
Autonomic Decompensation Proposed linkage within the distributed-network model; the intervening causal sequence has not been established in catatonia. Distributed psychomotor network model
Parakinetic Motor Output The distributed-network model proposes that orbitofrontal circuit disturbance can produce repetitive and imitative behavior.
Show evidence (3 references)
PMID:31174212 SUPPORT PRIMARY RESULT Human Clinical
"we found predominantly frontothalamic and corticostriatal abnormalities in SSD patients with catatonia"
Within a schizophrenia-spectrum sample, catatonia is associated with frontothalamic and corticostriatal imaging differences; residual confounding and etiological generalizability remain unresolved.
PMID:31174212 SUPPORT PRIMARY RESULT Human Clinical
"NCRS behavioral scores were associated with a joint structural and functional system that predominantly included cerebellar and prefrontal/cortical motor regions."
Adds the cerebellar and cortical motor components of the network and ties them to symptom severity.
PMID:42431537 SUPPORT REVIEW SYNTHESIS Human Clinical
"The best-supported mechanistic model to date comes from neuroimaging studies implicating cortico-striatal-thalamic, cortico-cerebellar, orbitofrontal, cingulate, and motor-premotor networks."
Establishes this set of networks as the best-supported mechanistic account, which is why it is modeled as the hub.
Hypokinetic Psychomotor Output
Reduced initiation of movement and speech, including akinesia, stupor and mutism, characterizes the hypokinetic presentation. Other motor abnormalities may accompany it, and excited signs may occur during the same illness. This clinical pattern is not itself evidence for a unique neurotransmitter deficit.
Downstream
Pneumonia Immobility increases risk of this respiratory complication; the source does not resolve the complete intervening pathway.
Deep venous thrombosis Reported as an increased-risk complication in patients with schizophrenia and catatonic stupor. The source does not establish the specific causal intermediates for this complication.
Pulmonary embolism Immobility increases risk of this respiratory complication; the source does not resolve the complete intervening pathway.
Rhabdomyolysis Immobility/stupor and rigidity can increase muscle-complication risk, including rhabdomyolysis; patient-level causal intermediates remain unresolved.
Pressure ulcer Prolonged immobility/stupor increases risk of pressure injury.
Mutism Failure to initiate activity is clinically expressed as this hypokinetic sign.
Stupor Failure to initiate activity is clinically expressed as this hypokinetic sign.
Reduced Oral Intake Reduced initiation and withdrawal can impair eating and drinking.
Akinesia Absent voluntary movement is a clinical expression of the hypokinetic dimension.
Show evidence (2 references)
PMID:32070914 SUPPORT PRIMARY RESULT Human Clinical
"The phenomenological profile of catatonia in this sample of cases of NMDAr-AbE was characterised by a preponderance of signs in the hypokinetic spectrum."
Names the hypokinetic spectrum as a distinguishable output and shows it predominating in a defined subgroup.
PMID:35861966 SUPPORT REVIEW SYNTHESIS Human Clinical
"The clinical picture of catatonia ranges from akinetic stupor to severe motoric excitement."
Places akinetic stupor at one end of the clinical range this node represents.
Hyperkinetic Psychomotor Output
Increased, non-purposeful motor activity is the hyperkinetic dimension of catatonia. It may fluctuate with hypokinetic signs within an episode. This dimension is distinct from qualitative abnormalities of movement, although both may coexist.
Downstream
Agitation Non-goal-directed agitation is a manifestation of the increased-motor-activity dimension.
Show evidence (2 references)
PMID:42431537 SUPPORT REVIEW SYNTHESIS Human Clinical
"catatonia is internally heterogeneous, with hypokinetic, hyperkinetic, and aberrant-volitional components that often overlap within the same episode"
The review distinguishes hyperkinetic from aberrant-volitional components while allowing overlap.
PMID:32070914 SUPPORT PRIMARY RESULT Human Clinical
"However, excitement often co-occurred in these patients suggesting that fluctuations in catatonic semiology may be frequent."
Empirical support for within-episode fluctuation between the two poles.
Parakinetic Motor Output
Mechanism confidence: Provisional
Qualitatively abnormal, context-inappropriate motor behavior is the parakinetic dimension of catatonia. A proposed lateral orbitofrontal circuit disturbance could contribute to repetitive or imitative behaviors. The circuit explanation is provisional and these signs need not imply increased overall motor activity.
Downstream
Motor stereotypy Repetitive or imitative movement is a clinical expression of the proposed abnormal motor-output process.
Echopraxia Repetitive or imitative movement is a clinical expression of the proposed abnormal motor-output process.
Echolalia Imitative speech is a clinical expression of the proposed abnormal motor-output process. The circuit explanation remains provisional.
Show evidence (2 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Catatonia can present as hypokinetic (reduced activity), hyperkinetic (elevated activity), or parakinetic (odd, purposeless motor behaviors unrelated to amount of motor activity)"
Distinguishes the qualitative motor dimension from overall activity.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"disruptions in the lateral orbitofrontal circuit could produce repetitive and mimicking behaviors"
Proposed circuit-to-behavior relationship, not a demonstrated universal mechanism.
Autonomic Decompensation
Clinically significant autonomic abnormalities define malignant catatonia. Hyperthermia, tachycardia and blood-pressure abnormalities may accompany any motor presentation. The condition is life-threatening and overlaps clinically with neuroleptic malignant syndrome; the relationship between the two syndromes remains debated.
Downstream
Fever Clinically significant autonomic dysfunction in malignant catatonia can manifest as this sign.
Tachycardia Clinically significant autonomic dysfunction in malignant catatonia can manifest as this sign.
Show evidence (2 references)
PMID:35861966 SUPPORT REVIEW SYNTHESIS Human Clinical
"Malignant catatonia describes catatonia that presents with clinically significant autonomic abnormalities including change in temperature, blood pressure, heart rate, and respiratory rate."
Defines the autonomic decompensation this node represents.
PMID:35861966 SUPPORT REVIEW SYNTHESIS Human Clinical
"Prompt recognition and treatment of catatonia are crucial because malignant catatonia may be fatal without treatment."
Records the outcome that makes this node the highest-stakes branch of the graph.
Reduced Oral Intake
Catatonic withdrawal and impaired initiation of activity may reduce eating and drinking, producing nutritional and fluid deficits.
Downstream
Malnutrition Insufficient intake can produce nutritional deficiency.
Show evidence (1 reference)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Nutritional deficiencies may occur due to the catatonic feature of withdrawal leading to poor oral intake."
Specifies an intermediate between withdrawal and nutritional complications.
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Pathograph

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Pathograph: causal mechanism network for Catatonia Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

25
Blood 2
Deep venous thrombosis HP:0002625 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Deep venous thrombosis (HP:0002625). HP:0002625 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
Lists deep vein thrombosis among the complications of catatonic stupor.
Disseminated intravascular coagulation HP:0005521 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Disseminated intravascular coagulation (HP:0005521). HP:0005521 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
Lists disseminated intravascular coagulation among the complications of catatonic stupor.
Cardiovascular 2
Tachycardia HP:0001649 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tachycardia (HP:0001649). HP:0001649 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In some cases, this can lead to a life-threatening elevation in blood pressure, heart rate and body temperature with a poor outcome."
The malignant-catatonia definition states the direction of change, not only an unspecified autonomic disturbance.
Pulmonary embolism HP:0002204 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pulmonary embolism (HP:0002204). HP:0002204 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
Lists pulmonary embolus among the complications of catatonic stupor.
Digestive 1
Malnutrition HP:0004395 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Malnutrition (HP:0004395). HP:0004395 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Nutritional deficiencies may occur due to the catatonic feature of withdrawal leading to poor oral intake."
Supports the nutritional complication and its clinical route.
Genitourinary 1
Urinary retention HP:0000016 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Urinary retention (HP:0000016). HP:0000016 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
The guideline names urinary retention among complications observed in the cited clinical cohort.
Head and Neck 1
Facial grimacing HP:0000273 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Facial grimacing (HP:0000273). HP:0000273 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:12384773 SUPPORT PRIMARY RESULT Human Clinical
"The disorder is characterized by qualitative hyperkinetic and akinetic psychomotor disturbances through acute psychotic episodes and debilitating symptoms in the long term, with psychomotor weakness, grimacing facial movements and apathy."
Reports grimacing facial movements as a persistent feature in the periodic-catatonia phenotype.
Immune 1
Pneumonia HP:0002090 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pneumonia (HP:0002090). HP:0002090 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
Names pneumonia among the complications carried by catatonic stupor in the cited cohort.
Integument 1
Pressure ulcer HP:0012399 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pressure ulcer (HP:0012399). HP:0012399 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
The guideline names decubitus ulcers among complications observed in the cited clinical cohort.
Metabolism 2
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In some cases, this can lead to a life-threatening elevation in blood pressure, heart rate and body temperature with a poor outcome."
The malignant-catatonia definition states the direction of change, not only an unspecified autonomic disturbance.
Dehydration HP:0001944 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dehydration (HP:0001944). HP:0001944 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
The guideline names dehydration among complications observed in the cited clinical cohort.
Musculoskeletal 2
Rigidity HP:0002063 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Rigidity (HP:0002063). HP:0002063 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32070914 SUPPORT PRIMARY RESULT Human Clinical
"The most prevalent signs were immobility/stupor (70%), mutism (67%), excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and rigidity (30%)."
Reports rigidity among the ascertained catatonic signs.
Rhabdomyolysis HP:0003201 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Rhabdomyolysis (HP:0003201). HP:0003201 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37039129 SUPPORT REVIEW SYNTHESIS Human Clinical
"increased risk of various infections (pneumonia, urinary tract infection and sepsis), disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia and..."
Lists rhabdomyolysis among the complications of catatonic stupor.
Nervous System 8
Mutism HP:0002300 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Mutism (HP:0002300). HP:0002300 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32070914 SUPPORT PRIMARY RESULT Human Clinical
"The most prevalent signs were immobility/stupor (70%), mutism (67%), excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and rigidity (30%)."
Quantifies mutism among the most prevalent catatonic signs in a defined cohort.
Akinesia HP:0002304 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Akinesia (HP:0002304). HP:0002304 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35861966 SUPPORT REVIEW SYNTHESIS Human Clinical
"The clinical picture of catatonia ranges from akinetic stupor to severe motoric excitement."
Establishes akinetic stupor as a recognized presentation of catatonia.
Abnormal posturing HP:0002533 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Abnormal posturing (HP:0002533). HP:0002533 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37236789 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Posturing (spontaneous assumption of postures sustained against gravity)"
Defines active posturing as a distinct catatonic sign.
Motor stereotypy HP:0000733 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Motor stereotypy (HP:0000733). HP:0000733 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:32070914 SUPPORT PRIMARY RESULT Human Clinical
"The most prevalent signs were immobility/stupor (70%), mutism (67%), excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and rigidity (30%)."
Reports stereotypies among the ascertained catatonic signs.
Negativism HP:0410291 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Negativism (HP:0410291). HP:0410291 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37236789 SUPPORT REVIEW SYNTHESIS Human Clinical
"Negativism (resistance to instructions, which might even entail doing the opposite to them)"
The DSM-5-TR criterion definition, from the BAP concise guideline's summary of diagnostic criteria.
Echolalia HP:0010529 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Echolalia (HP:0010529). HP:0010529 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37236789 SUPPORT REVIEW SYNTHESIS Human Clinical
"Echolalia (repetition of another person's speech)"
The DSM-5-TR criterion definition for echolalia as a catatonic sign.
Agitation HP:0000713 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Agitation (HP:0000713). HP:0000713 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35861966 SUPPORT REVIEW SYNTHESIS Human Clinical
"The clinical picture of catatonia ranges from akinetic stupor to severe motoric excitement."
Establishes severe motoric excitement as a recognized pole of the syndrome.
Echopraxia HP:0020124 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Echopraxia (HP:0020124). HP:0020124 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37236789 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Echopraxia (mimicry of another person's movements)"
Listed among DSM-5-TR catatonic signs in the concise guideline.
Other 4
Stupor
Needs term: OLS4 HP search on 2026-10-04 for 'stupor' returned coma and akinetic mutism, which are not equivalent to catatonic stupor. Search endpoint: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=stupor. The descriptor is retained without a misleading ontology equivalence.
Show evidence (1 reference)
PMID:37236789 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Stupor (lack of responsiveness to the environment)"
Listed among DSM-5-TR catatonic signs in the concise guideline.
Catalepsy
Needs term: OLS4 HP search on 2026-10-04 for 'catalepsy' returned no hits. Search endpoint: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=catalepsy. The descriptor is retained without a misleading ontology equivalence.
Show evidence (1 reference)
PMID:37236789 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Catalepsy (a posture induced by an external agent is sustained against gravity)"
Listed among DSM-5-TR catatonic signs in the concise guideline.
Waxy flexibility
Needs term: OLS4 HP search on 2026-10-04 for 'waxy flexibility' returned no hits. Search endpoint: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=waxy%20flexibility. The descriptor is retained without a misleading ontology equivalence.
Show evidence (1 reference)
PMID:37236789 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Waxy flexibility (steady, even resistance to repositioning)"
Listed among DSM-5-TR catatonic signs in the concise guideline.
Mannerism
Needs term: OLS4 HP search on 2026-10-04 for 'mannerism' returned motor stereotypy and broader behavior terms, none equivalent to a caricature of a normal motor act. Search endpoint: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=mannerism. The descriptor is retained without a misleading ontology equivalence.
Show evidence (1 reference)
PMID:37236789 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Mannerism (caricature of a normal motor act)"
Listed among DSM-5-TR catatonic signs in the concise guideline.
🧬

Genetic Associations

1
Chromosome 15q15 periodic catatonia susceptibility locus (Periodic catatonia, a familial sub-phenotype with recurrent hyperkinetic and akinetic psychomotor episodes, maps to a major susceptibility locus on chromosome 15q15, confirmed in a second independent genome scan. The linkage study did not identify a causal gene, and it demonstrated genetic heterogeneity between families, so this is recorded as a susceptibility locus rather than as a catatonia gene.)
relationship_type: SUSCEPTIBILITY
Show evidence (2 references)
PMID:12384773 SUPPORT Human Clinical
"Here, we confirm mapping of a major gene locus on chromosome 15q15 in a second genome scan in a new set of four multiplex families."
Independent confirmation of the linkage signal in a new family set.
PMID:12384773 SUPPORT Human Clinical
"Analysis of individual families showed that one large family showed linkage, whereas two others could be clearly excluded, confirming genetic heterogeneity."
The heterogeneity caveat: the locus explains some families and is excluded in others, so it cannot be read as a general catatonia gene.
💊

Medical Actions

20
Lorazepam
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: lorazepam CHEBI:6539 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses lorazepam (CHEBI:6539). CHEBI:6539 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Lorazepam is a positive allosteric modulator of GABA-A receptors and a first-line treatment for catatonia. In an open prospective study, signs resolved in 16 of 21 patients completing a lorazepam trial; this is an uncontrolled response proportion. Treatment is titrated to clinical response and tolerability, with attention to sedation and respiratory effects. Benzodiazepines are tapered rather than stopped abruptly because withdrawal can precipitate recurrence. Response varies with clinical context and may be less reliable in chronic catatonia associated with schizophrenia. When catatonia follows benzodiazepine withdrawal, a benzodiazepine can be reinstated. Older adults may respond to lower doses.
Mechanism Target:
MODULATES Cortical GABA-A Receptor-Mediated Inhibition Deficit — Lorazepam enhances GABA-A receptor signaling. Its clinical efficacy is compatible with a GABAergic contribution to catatonia but does not demonstrate restoration of receptor density or establish a universal inhibitory deficit.
Show evidence (1 reference)
PMID:37039129 SUPPORT INDIRECT REVIEW SYNTHESIS Human Clinical
"Lorazepam is a non-selective positive allosteric modulator of GABA-A receptors."
The drug action is established; its linkage to the proposed disease deficit is indirect.
Show evidence (6 references)
PMID:8686484 SUPPORT PRIMARY RESULT Human Clinical
"In 16 of 21 patients (76%) who received a complete trial of lorazepam (11 with initial intravenous challenge), catatonic signs resolved."
The prospective, quantitatively monitored response rate underpinning first-line status.
PMID:37236789 SUPPORT REVIEW SYNTHESIS Human Clinical
"First-line treatment comprises benzodiazepines and/or electroconvulsive therapy. The benzodiazepine of choice is lorazepam, which is sometimes used in very high doses."
Current guideline statement of first-line status and the drug of choice.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Benzodiazepines for catatonia should not be stopped abruptly but rather tapered down."
Addresses withdrawal and recurrence risk.
+ 3 more references
Electroconvulsive therapy
Action: electroconvulsive therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is electroconvulsive therapy (NCIT:C93303). NCIT:C93303 is a clinical intervention from the NCI Thesaurus. Ontology label: Electroconvulsive Therapy NCIT:C93303
Platform: Device
ECT is a first-line option alongside benzodiazepines and is recommended when benzodiazepines have not produced remission. Choice and urgency depend on severity, underlying illness, tolerability and availability. Malignant catatonia may require urgent ECT when lorazepam is not rapidly effective. Four lorazepam nonresponders improved with ECT in an open prospective study, but this does not identify the biological mechanism of ECT. Severe respiratory disease may favor ECT as the initial treatment. Selected patients require maintenance ECT to prevent relapse.
Show evidence (5 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where benzodiazepines have not resulted in remission, ECT should be used."
Guideline recommendation after inadequate benzodiazepine response.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"if benzodiazepines are not rapidly effective, ECT should be started within 48–72 h following the onset of malignant catatonia"
Addresses the urgency of escalation in malignant catatonia.
PMID:8686484 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Four patients failing lorazepam responded promptly to ECT."
Small uncontrolled treatment observation, not evidence of a particular network or transmitter mechanism.
+ 2 more references
Treatment of the underlying condition
Action: Therapeutic ProcedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Therapeutic Procedure (NCIT:C49236). NCIT:C49236 is a clinical intervention from the NCI Thesaurus. NCIT:C49236
Platform: Other
Treat an identified underlying psychiatric or medical disorder alongside catatonia-specific treatment and supportive care. Management depends on the cause and may include immunotherapy for autoimmune encephalitis or removal of a precipitating medication. Catatonia treatment need not await every investigation result.
Show evidence (2 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Catatonia treatment should consist of specific treatment for the catatonia, treatment of any underlying disorder and prevention and management of complications of catatonia."
The guideline explicitly describes all three components of management.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Treatment for catatonia should be instituted quickly after identification of catatonia and it is not always necessary to await results of all investigations before commencing treatment."
Etiological evaluation and urgent symptomatic treatment can proceed together.
Amantadine and memantine
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: amantadine CHEBI:2618 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses amantadine (CHEBI:2618). CHEBI:2618 is a therapeutic agent from Chemical Entities of Biological Interest. memantine CHEBI:64312 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses memantine (CHEBI:64312). CHEBI:64312 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Amantadine or memantine may be considered when first-line benzodiazepine and ECT approaches are unavailable, cautioned, ineffective or only partly effective. Both antagonize NMDA receptors; amantadine also has dopaminergic effects. Proposed circuit explanations remain hypotheses. Reported benefits mainly come from case reports and small series, with possible publication bias. Their use does not establish NMDA hyperactivity as a general cause of catatonia or a mechanism-specific treatment for anti-NMDA receptor encephalitis. Amantadine requires particular caution in patients at seizure risk or with renal disease.
Show evidence (4 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where first-line therapies for catatonia are unavailable, cautioned, ineffective or only partially effective, consider a trial of an NMDA receptor antagonist, either amantadine or memantine."
Recommendation includes the availability and tolerability of first-line options, not just lorazepam failure.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"A bias towards the non-reporting of negative results must be considered, making the lack of RCTs and controlled studies an important shortcoming."
The guideline qualifies its synthesis of amantadine and memantine reports.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Amantadine lowers the seizure threshold and should be used cautiously in patients at increased risk for seizures, including epilepsy and anti-NMDA receptor antibody encephalitis"
Clinical caution is particularly relevant to the autoimmune subgroup.
+ 1 more reference
Antipsychotic medication review
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Platform: Other
Antipsychotics can induce or worsen catatonia and increase concern for neuroleptic malignant syndrome. Avoid them when there is no underlying psychotic disorder; discontinue dopamine antagonists in malignant catatonia. When treating coexisting psychosis, the guideline allows cautious second-generation antipsychotic use after an individual assessment, gradual titration and consideration of a benzodiazepine. For antipsychotic-induced catatonia, discontinuation is the primary intervention; if an antipsychotic remains necessary after treatment, restart cautiously.
Show evidence (4 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Antipsychotic medications should be avoided where there is no underlying psychotic disorder."
Avoidance is context-specific.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In malignant catatonia, discontinue all dopamine antagonists."
Malignant catatonia requires a stronger avoidance recommendation.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"If antipsychotic medications are used, a SGA should be used with gradual titration, and co-administration of a benzodiazepine should be considered."
The guideline permits carefully assessed treatment of underlying psychosis.
+ 1 more reference
Supportive care and prevention of complications
Action: Supportive CareNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Supportive Care (NCIT:C15747). NCIT:C15747 is a clinical intervention from the NCI Thesaurus. NCIT:C15747
Platform: Other
Provide hydration and nutritional support according to need, assess swallowing and consider assisted feeding, prevent pressure injury, and assess venous thromboembolism risk with prophylaxis when appropriate. Monitoring and supportive care accompany treatment of catatonia and its underlying cause.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Guidance has been developed for averting such complications, which include recommendations such as pharmacological thromboprophylaxis, frequent assessment of pressure areas, stretching to avoid muscle contractures and consideration of artificial feeding"
Guideline synthesis of measures that prevent complications of prolonged catatonia.
Clozapine in selected contexts
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: clozapine CHEBI:3766 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses clozapine (CHEBI:3766). CHEBI:3766 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Restarting clozapine is recommended when its withdrawal precipitates catatonia, if clinically feasible, with re-titration after an interruption. ECT is another option. Clozapine may also be considered for chronic mild catatonia associated with schizophrenia. These indications do not justify routine antipsychotic treatment of catatonia without psychosis; the evidence is largely uncontrolled.
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where catatonia has resulted from clozapine withdrawal, restart clozapine if possible and, if necessary, use ECT."
Specific withdrawal-related recommendation.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"If catatonia is chronic and mild in the context of schizophrenia, consider a trial of clozapine."
A separate, restricted clinical context for clozapine.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"If clozapine therapy is interrupted for more than 48 hours, re-titration from a typical starting dose"
Re-initiation must account for the interruption rather than simply restoring a previous maintenance dose.
Lithium maintenance for periodic catatonia
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: lithium(1+) CHEBI:49713 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses lithium(1+) (CHEBI:49713). CHEBI:49713 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Lithium may be considered to prevent recurrent episodes of periodic catatonia. This maintenance indication rests on case reports and small case series, rather than controlled proof of efficacy for catatonia generally.
Show evidence (2 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In the maintenance phase of periodic catatonia, consider prophylactic treatment with lithium."
Conditional maintenance recommendation.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Lithium is the most frequently reported agent used in the maintenance of periodic catatonia, but even this evidence relies only on case reports and small case series"
States the evidence limitation.
Zolpidem
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: zolpidem CHEBI:10125 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses zolpidem (CHEBI:10125). CHEBI:10125 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Zolpidem has been used as a diagnostic or therapeutic challenge and as an alternative treatment in case reports, including after inadequate lorazepam or ECT response. Reported effects are often transient; this is not an established substitute for first-line treatment.
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"When a diagnosis of catatonia is uncertain, a diagnostic challenge using zolpidem may be considered."
Conditional diagnostic use.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Mastain et al. (1995) described a serendipitous dramatic response to oral zolpidem 10 mg in a woman with a subcortical stroke whose catatonia was largely unresponsive to lorazepam or ECT."
The guideline describes an uncontrolled treatment observation.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"The response is transitory, as with benzodiazepines, and is usually observed for 3–6 h"
Limits interpretation of the reported response duration.
Carbamazepine
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: carbamazepine CHEBI:3387 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses carbamazepine (CHEBI:3387). CHEBI:3387 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Carbamazepine is a lower-evidence option when first-line treatments and NMDA receptor antagonists are unavailable, cautioned or insufficient. Evidence consists of case reports and small series, often in patients with mood disorders; interactions and adverse effects require consideration.
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Three articles have reported using carbamazepine to treat catatonia in seven cases"
Small uncontrolled evidence base.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Carbamazepine is less commonly used due to concerns of side effects and drug-drug interactions."
Explains a limitation of this alternative.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine, valproate, topiramate or a SGA."
Low-grade BAP recommendation for later-line options, not a head-to-head demonstration of efficacy.
Valproic acid
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: valproic acid CHEBI:39867 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses valproic acid (CHEBI:39867). CHEBI:39867 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Valproate has been used as an adjunct or alternative in catatonia, including excited presentations. The evidence is limited to case reports and series. It may also address a comorbid mood disorder; reproductive risks matter when selecting treatment.
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Valproic acid use in catatonia has been reported in four papers in which five patients were suffering with psychoses, mostly schizophrenia spectrum in nature. In three instances, excited catatonia was noted as part of the presentation."
Describes the small and selected reported clinical population.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Valproate may be a good option for catatonia patients with comorbid bipolar disorder; however, caution should be used in women of childbearing potential due to the risk for teratogenic effects and polycystic ovary syndrome."
Contextual benefit and safety considerations from expert synthesis.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine, valproate, topiramate or a SGA."
Low-grade BAP recommendation for later-line options, not a head-to-head demonstration of efficacy.
Topiramate
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: topiramate CHEBI:63631 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses topiramate (CHEBI:63631). CHEBI:63631 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Topiramate has been reported as an adjunct to benzodiazepines in a small case series. It is a lower-evidence option when established treatments and NMDA antagonists cannot be used or have been insufficient.
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Another case series involving four cases highlighted the benefits of topiramate in the treatment of catatonia"
Identifies the limited study design.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Topiramate was used as an adjunctive treatment along with a benzodiazepine."
Supports adjunctive rather than established monotherapy use.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine, valproate, topiramate or a SGA."
Low-grade BAP recommendation for later-line options, not a head-to-head demonstration of efficacy.
Repetitive transcranial magnetic stimulation
Action: Repetitive Transcranial Magnetic StimulationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Repetitive Transcranial Magnetic Stimulation (NCIT:C154664). NCIT:C154664 is a clinical intervention from the NCI Thesaurus. NCIT:C154664
Platform: Device
rTMS is an investigational alternative when ECT is indicated but unavailable. Case reports and small series suggest benefit, but establish neither comparative efficacy nor the optimal stimulation target.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where ECT is indicated but unavailable, consider treatment with rTMS or tDCS."
Conditional recommendation supported mainly by case reports and case series; not established equivalence to ECT.
Transcranial direct current stimulation
Action: Transcranial Direct Current StimulationNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Transcranial Direct Current Stimulation (NCIT:C129862). NCIT:C129862 is a clinical intervention from the NCI Thesaurus. NCIT:C129862
Platform: Device
tDCS is an investigational neuromodulation option when ECT is indicated but unavailable. Available case reports and series do not establish its comparative efficacy.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where ECT is indicated but unavailable, consider treatment with rTMS or tDCS."
Conditional recommendation supported mainly by case reports and case series; not established equivalence to ECT.
Dopaminergic agents: conflicting guidance
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: levodopa CHEBI:15765 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses levodopa, annotated with L-dopa (CHEBI:15765). CHEBI:15765 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Levodopa and dopamine agonists have been tried in isolated cases. The BAP guideline lists them as low-evidence later-line possibilities, whereas the 2025 APA resource document discourages them because of reported worsening of psychosis. They are not established routine treatments for catatonia, and their use does not prove a general dopamine-deficiency mechanism.
Show evidence (2 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine, valproate, topiramate or a SGA."
BAP conditional, low-grade recommendation.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Dopamine agonists, including stimulants and carbidopa-levodopa, have also been used with some success for catatonia, though nearly all patients have noted worsening of psychotic symptoms; as such, they are not recommended"
The APA authors draw a different clinical recommendation from the limited reports; the entry preserves this disagreement.
Psychological support for mild catatonia in autism
Action: PsychotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Psychotherapy (NCIT:C15308). NCIT:C15308 is a clinical intervention from the NCI Thesaurus. NCIT:C15308
Platform: Behavioral / lifestyle
In autistic people with mild catatonia, psychological interventions and/or lorazepam may be considered. Moderate or severe presentations require consideration of benzodiazepines and/or ECT. Assessment must first establish a marked change from the individual's baseline autistic traits.
Show evidence (1 reference)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"First-line interventions in mild cases of catatonia are psychological interventions and/or lorazepam, but the standard treatments for catatonia (i.e. benzodiazepines in escalating dosages and/or bilateral ECT) should be considered in moderate to severe cases."
This recommendation occurs in the guideline section on autism, not as a general substitute for treatment of severe catatonia.
Oxazepam
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: oxazepam CHEBI:7823 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses oxazepam (CHEBI:7823). CHEBI:7823 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Oxazepam improved severe psychomotor retardation and mutism in a small double-blind crossover comparison with lorazepam. The study population was defined by these symptoms, so its findings should not be treated as proof of equivalence across all catatonia presentations. Lorazepam remains the usual first choice.
Show evidence (3 references)
PMID:10435212 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Twenty-one hospitalized patients with severe psychomotor retardation and mutism were treated with 2 mg LO and 60 mg OX in a double-blind crossover study design."
Defines the selected study population and comparator design.
PMID:10435212 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Both benzodiazepines significantly reduced psychomotor symptoms."
Supports symptom improvement without a general noninferiority claim.
PMID:10435212 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"The second time, however, LO was significantly better compared with OX in alleviating the target symptoms."
Preserves the sequence-related difference rather than asserting equal effects.
Ketamine and esketamine
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: ketamine CHEBI:6121 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses ketamine (CHEBI:6121). CHEBI:6121 is a therapeutic agent from Chemical Entities of Biological Interest. esketamine CHEBI:60799 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses esketamine (CHEBI:60799). CHEBI:60799 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Ketamine and esketamine are experimental treatments supported by a small, heterogeneous published case literature, predominantly involving retarded catatonia and underlying mood disorders. A systematic review assembled 25 patients; reported improvements do not establish controlled efficacy or general safety. Dissociative adverse effects can limit treatment.
Show evidence (3 references)
PMID:39098303 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Twenty articles were included, encompassing a total of 25 catatonic patients receiving ketamine or esketamine."
Small systematic aggregation of the published clinical literature.
PMID:39098303 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"patients mostly exhibited manifestations compatible with the retarded subtype of catatonia. Mood disorders were the most prevalent underlying diagnoses."
Limits applicability to the reported clinical mix.
PMID:39098303 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"Only one patient discontinued treatment due to intolerable dissociative effects."
Reports an observed tolerability limitation; the small dataset cannot exclude other risks.
Sodium oxybate under investigation
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: sodium oxybate CHEBI:749298 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses sodium oxybate (CHEBI:749298). CHEBI:749298 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Sodium oxybate is being evaluated against continued lorazepam in the Laborit randomized trial for lorazepam-resistant catatonia associated with psychiatric disorders. The published protocol proposes GABA-B-mediated benefit but reports no randomized efficacy results. Its restricted eligibility and respiratory monitoring requirements limit generalization, particularly to malignant or medically caused catatonia.
Show evidence (4 references)
PMID:40705436 SUPPORT DIRECT BACKGROUND Human Clinical
"This study aims to provide robust evidence on the efficacy and safety of sodium oxybate for treating catatonia unresponsive to lorazepam"
A research objective, not an established treatment effect.
PMID:40705436 SUPPORT DIRECT BACKGROUND Human Clinical
"We hypothesize that pharmacological therapies, aimed at increasing GABA-B–mediated neurotransmission, could be effective in patients with lorazepam-resistant catatonia."
Mechanistic rationale remains a hypothesis.
PMID:40705436 SUPPORT DIRECT BACKGROUND Human Clinical
"This study focuses on semiacute catatonic episodes caused by either psychotic or affective disorders; hence, chronic catatonia and patients with underlying somatic disorders are excluded."
Defines the protocol population.
+ 1 more reference
Patient and caregiver education
Platform: Behavioral / lifestyle
Explain that catatonia is treatable and can impair communication and voluntary initiation. Teach families to recognize new motor or behavioral changes and recurrence, and coordinate psychiatric, neurological, nursing and rehabilitation care.
Show evidence (1 reference)
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK430842/ SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"After remission, families should be counseled on monitoring for recurrence, particularly in individuals with mood disorders or those with a prior catatonic episode."
Practical follow-up advice from the clinical overview.
🔬

Diagnosis

5
Clinical assessment and diagnostic criteria
Diagnosis is clinical, requiring three or more catatonic signs under DSM-5-TR or ICD-11. DSM-5-TR lists stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerism, stereotypy, agitation, grimacing, echolalia and echopraxia. Observation, elicitation and physical examination are complementary, and collateral history helps identify fluctuating signs and underlying conditions. In autism, a marked change from baseline is required.
Show evidence (2 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Catatonia should be diagnosed based on the presence of three or more catatonic signs, as in DSM-5-TR or ICD-11."
The guideline recommends a clinical sign threshold; a response to medication is not required.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Diagnosis of catatonia in autism spectrum disorder requires a marked change from baseline presentation."
Distinguishes a new catatonic syndrome from overlapping baseline autistic features.
Bush-Francis Catatonia Rating Scale
The BFCRS is a widely used instrument for screening and quantifying catatonic signs and tracking treatment response. Its first 14 items form the screening instrument; the full scale has 23 items. Scale findings should be translated into diagnostic criteria, since definitions of motor signs differ between instruments.
Show evidence (4 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"The first 14 items of the BFCRS comprise the Bush-Francis Catatonia Screening Instrument (BFCSI)."
Defines the screening subset.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"The full 23-item scale evaluates all ICD-11 catatonia criteria."
Defines the full scale coverage.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"The results of a catatonia rating scale should be converted to diagnostic criteria for clinical diagnosis"
Scale thresholds and formal diagnostic criteria are not interchangeable.
+ 1 more reference
Lorazepam challenge test
A lorazepam challenge can support an uncertain diagnosis and help predict benzodiazepine response. A reduction in catatonic signs supports catatonia but is not fully specific: nonconvulsive status epilepticus and stiff-person syndrome may also improve. A negative response does not by itself establish another diagnosis.
Show evidence (4 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"A positive response to a lorazepam challenge, commonly defined as a 50% reduction in catatonic signs on a standardised scale, makes a diagnosis of catatonia more likely, but it is not 100% specific."
The guideline supplies an operational response threshold and its specificity limit.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Challenge tests are useful in many situations"
The challenge supplements clinical assessment.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"stiff person syndrome and NCSE are likely to improve with a lorazepam challenge."
Benzodiazepine responsiveness also occurs in important mimics.
+ 1 more reference
Investigation of underlying conditions and mimics
Investigations are selected according to history, examination, severity and suspected causes. A first or unexplained episode warrants consideration of brain CT or MRI and serum and CSF neuronal autoantibodies, including NMDA receptor antibodies. EEG is considered where seizures, encephalitis or nonconvulsive status epilepticus are suspected. These tests investigate causes and mimics; none is a general diagnostic biomarker for catatonia.
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In patients experiencing a first episode of catatonia or where the diagnosis underlying catatonia is unclear, consider a CT or MRI scan of the brain."
Neuroimaging is part of etiological evaluation rather than a confirmatory catatonia test.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In patients experiencing a first episode of catatonia or where the diagnosis underlying catatonia is unclear, consider assessing for the presence of antibodies to the NMDA receptor and other relevant autoantibodies in serum and CSF."
Supports testing for autoimmune causes when the presentation warrants investigation.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In patients with risk factors for seizures, possible evidence of a seizure or possible encephalitis, consider performing an EEG (with continuous monitoring if available)."
Scopes EEG to clinical indications.
Assessment of medical complications
Physical assessment includes hydration, nutritional intake, temperature and other vital signs, pressure areas, and signs of venous thrombosis. Laboratory investigations and monitoring are guided by suspected complications. Reduced responsiveness should not be assumed to mean absent awareness or deliberate refusal of care.
Show evidence (2 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Physical examination should include assessment for catatonic signs, signs of medical conditions that may have led to the catatonia and signs of medical complications of catatonia."
Medical examination addresses both causes and consequences.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"When assessing a patient with catatonia, clinicians should interact with the person as if they are able to understand what is being said to them."
Impaired motor or verbal output does not establish absent comprehension.
📊

Prevalence

5
Clinical samples worldwide (psychiatric and medical settings)
Unknown 9000.0 per 100,000 (6900.0–11700.0) >1 in 1,000
Pooled clinical-sample proportion of 9.0% (95% CI 6.9-11.7%; I2 = 98%) across heterogeneous psychiatric and medical settings. The underlying studies have differing designs and ascertainment windows, so a common point-prevalence time frame is not assigned. This is not a general-population estimate. The abstract and main tables disagree slightly on total sample size; no combined denominator is inferred.
Show evidence (1 reference)
PMID:29140521 SUPPORT PRIMARY RESULT Human Clinical
"mean catatonia prevalence was 9.0% (k = 80, n = 110764; 95% CI = 6.9-11.7, I2 = 98%, publication bias P < .01)"
The pooled meta-analytic estimate, quoted with its confidence interval and heterogeneity statistic.
South London and Maudsley catchment population, London, UK, 2007-2016; clinician-diagnosed catatonia
Annual Incidence 10.6 per 100,000 (10.0–11.1) person-years 1–9 per 10,000 per year
Counts new episodes, including recurrent episodes in the same person. Ascertainment required a clinical diagnosis and documented catatonic features; retrospective recognition and referral to psychiatric services affect capture. This local estimate is not worldwide incidence and uses a broader case definition than the later DSM-5-TR reanalysis.
Show evidence (1 reference)
PMID:35135642 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"giving an incidence of 10.6 (95% CI 10.0–11.1) episodes per 100 000 person-years."
The full results identify the catchment-specific episode rate and confidence interval.
South London and Maudsley catchment population, London, UK, 2007-2016; DSM-5-TR reanalysis
Annual Incidence 4.34 per 100,000 (3.98–4.72) person-years 1–9 per 100,000 per year
Reanalysis of the same London data using DSM-5-TR criteria, counting each new episode separately, including recurrences. This is not an independent cohort or a first-onset incidence rate.
Show evidence (1 reference)
PMID:39789943 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"This represents an incidence of 4.34 (95% CI 3.98 to 4.72) catatonic episodes per 100,000 person-years."
The primary reanalysis provides a stricter case-definition estimate.
Individuals with autism spectrum disorder in heterogeneous research samples
Unknown 10400.0 per 100,000 (5800.0–18000.0) >1 in 1,000
Pooled proportion across seven nonoverlapping samples comprising 969 individuals, with substantial heterogeneity and mixed cross-sectional and longitudinal designs. The shared measure is not a population point prevalence. Catatonia requires a new onset or marked worsening of symptoms relative to the individual autistic baseline.
Show evidence (1 reference)
PMID:34906264 SUPPORT PRIMARY RESULT Human Clinical
"Our meta-analysis showed that 10.4% (5.8-18.0 95%CI) of individuals with ASD have catatonia."
The systematic review computes a pooled proportion from selected ASD research samples; it does not estimate a worldwide population rate.
Published NMDA receptor antibody encephalitis case reports
Unknown 60000.0 per 100,000 >1 in 1,000
The review retrospectively applied a two-core-sign screening threshold to 189 individuals in 139 published reports. Its 60% proportion describes selected case literature, with ascertainment and publication bias; it is neither population prevalence nor a defensible upper bound on that prevalence.
Show evidence (1 reference)
PMID:32070914 SUPPORT PRIMARY RESULT Human Clinical
"Catatonia was present in 60% of these cases."
The proportion of NMDA receptor antibody encephalitis cases meeting catatonia criteria in this systematic review.
🔀

Differential Diagnoses

12

Conditions with similar clinical presentations that must be differentiated from Catatonia:

Neuroleptic malignant syndrome
Overlapping Features Neuroleptic malignant syndrome overlaps with malignant catatonia in rigidity, hyperthermia, altered mental state and autonomic dysfunction. Some experts consider dopamine-blocker-associated NMS a form of malignant catatonia.
Distinguishing Features
  • A temporal relationship to a dopamine receptor blocking medication supports NMS; malignant catatonia can occur without this exposure.
  • Suspected NMS requires immediate cessation of dopamine blocking medications and urgent treatment.
Show evidence (2 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"many experts consider neuroleptic malignant syndrome (NMS) to be a type of malignant catatonia that is precipitated by dopamine receptor blocking agents."
The resource document describes the exposure relationship and diagnostic overlap.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"When NMS is suspected, immediate cessation of antipsychotic and other dopamine blocking medications is imperative."
Identifies an immediate management implication of this differential.
Delirium
Overlapping Features Hypoactive delirium can resemble hypokinetic catatonia, and hyperactive delirium can resemble excited catatonia. The conditions can coexist; diagnostic manuals differ in how this is represented.
Distinguishing Features
  • Fluctuating arousal, impaired attention and cognitive disturbance favor delirium; additional catalepsy, posturing or echophenomena support assessment for coexisting catatonia.
  • An EEG may support delirium assessment, but does not replace clinical evaluation.
Show evidence (3 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Distinguishing features of delirium include impaired or fluctuating level of arousal, attention, and other cognitive disturbances. EEG can be helpful to confirm the diagnosis of delirium."
Supports the cognitive distinction in hyperactive presentations.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Classic findings more specific to catatonia are often helpful in identifying catatonia in patients with or at risk for delirium."
Supports assessment for both conditions rather than treating them as mutually exclusive.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"the ICD-11 recognizes catatonia as a distinct condition and allows for the co-diagnosis of both delirium and catatonia if they occur simultaneously."
Clarifies that the nosological distinction is not a biological exclusion.
Akinetic mutism and abulia
Overlapping Features Reduced volition after neurological injury can markedly reduce spontaneous movement and speech, resembling hypokinetic catatonia.
Distinguishing Features
  • Neurological injury and severe reduction in spontaneous movement and speech support an abulic or akinetic-mutism syndrome.
  • Additional positive catatonic signs, particularly catalepsy, posturing or echophenomena, favor a catatonic component; a lorazepam response alone is not a specific discriminator.
Show evidence (2 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"This disorder, characterized by reduced or absent volition, is typically due to neurologic injury affecting the ventromedial prefrontal cortex or anterior cingulate cortex (e.g., stroke, traumatic brain injury). Patients exhibit severe reductions in spontaneous movement and speech, which can..."
Describes the neurological context and clinical overlap without treating reduced speech as an exclusion.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"the positive features of catatonia (such as echophenomena, catalepsy and posturing) may have greater discriminatory value than some of the negative features (such as mutism and stupor). Challenge tests are useful in many situations"
General differential principle from the BAP guideline, not a test validated specifically against abulia.
Late-stage Parkinson disease
Overlapping Features Advanced Parkinson disease may cause immobility, rigidity and markedly reduced speech that resemble hypokinetic catatonia.
Distinguishing Features
  • Established Parkinson disease, resting tremor, postural instability, levodopa responsiveness and supportive dopamine transporter imaging help distinguish the underlying movement disorder.
  • These findings do not establish a shared degenerative mechanism for catatonia.
Show evidence (1 reference)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"These patients have a known diagnosis of PD and other distinguishing features of PD, including resting tremor, positive response to levodopa and postural instability, and/or a positive dopamine transporter scan"
The document identifies disease history and parkinsonian features as discriminators, not a universal catatonia mechanism.
Locked-in syndrome
Overlapping Features Patients can be immobile and mute while retaining the motivation to communicate.
Distinguishing Features
  • Attempts to communicate through preserved eye movements support locked-in syndrome.
  • Brain MRI can identify the responsible brainstem lesion.
Show evidence (2 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"These patients are often motivated to try to communicate with eye movements (which may be their only residual voluntary movements)"
Identifies a useful bedside feature without claiming every patient retains identical movements.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Locked-in syndrome is caused by brainstem lesions identified on brain MRI."
Supports structural imaging in the differential.
Serotonin syndrome
Overlapping Features Serotonin syndrome can resemble malignant catatonia through autonomic instability, hyperthermia and rigidity.
Distinguishing Features
  • A history of serotonergic agents and their doses is central to assessment.
  • Hyperreflexia, myoclonus and gastrointestinal symptoms support serotonin syndrome.
Show evidence (1 reference)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Hyperreflexia, myoclonus, and gastrointestinal symptoms can help to identify SS. Quantification of use and doses of all serotoninergic agents taken prior to presentation is necessary."
Provides specific distinguishing features and the relevant exposure history.
Stiff-person syndrome
Overlapping Features Muscle stiffness and spasms can limit movement and resemble catatonic rigidity. Both syndromes may improve with benzodiazepines.
Distinguishing Features
  • Emotional stress can exacerbate stiffness and spasms in stiff-person syndrome.
  • Preserved speech and cognition are typical, and elevated glutamic acid decarboxylase antibodies support the diagnosis.
  • Benzodiazepine responsiveness does not separate these conditions.
Show evidence (1 reference)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"The condition is exacerbated by emotional stress. Symptoms such as limited movement and positive response to benzodiazepines in SPS can somewhat resemble hypoactive catatonia. SPS differs from catatonia in that these patients are verbal and are typically fully cognitively intact. A diagnosis of..."
Supports clinical and antibody distinctions while qualifying the nonspecific treatment response.
Akathisia
Overlapping Features Motor restlessness can resemble excited catatonia, including after dopamine blocking medication exposure.
Distinguishing Features
  • Patients often describe inner restlessness and discomfort driving the movements.
  • Other catatonic signs are usually absent.
Show evidence (2 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"patients with akathisia will often describe an inner state of restlessness and discomfort that leads to and perpetuates the motor symptoms."
Supports the subjective restlessness distinction.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"patients with akathisia will not typically exhibit any other signs of catatonia."
Qualifies the distinction as typical rather than absolute.
Major neurocognitive disorders
Overlapping Features Advanced neurocognitive disorders may cause hypokinesis and mutism. Catatonia can also occur as a superimposed syndrome.
Distinguishing Features
  • Longitudinal cognitive decline across multiple domains supports an underlying neurocognitive disorder.
  • Posturing, catalepsy and waxy flexibility suggest coexisting catatonia rather than dementia alone.
Show evidence (2 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"In later stages of major neurocognitive disorder (MNCD)/dementia, patients can develop hypokinesis and mutism. However, they do not develop classic specific catatonia symptoms such as posturing, catalepsy and waxy flexibility unless comorbid catatonia is present."
Supports assessment for a superimposed catatonic syndrome.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Obtaining a chronological history of clinical progression can be clarifying, given that most MNCDs tend to develop and worsen over time."
Supports the longitudinal distinction without claiming all catatonia is acute or episodic.
Mania
Overlapping Features Mania and hyperkinetic catatonia can both produce agitation, excitation and excessive or disorganized speech. Severe mania may coexist with catatonia.
Distinguishing Features
  • Manic agitation may be goal-directed, whereas catatonic agitation is not.
  • The presence of mania does not exclude additional catatonic signs.
Show evidence (1 reference)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"One distinguishing feature is that agitation in catatonia is not goal-directed, whereas a manic episode may include goal-directed agitation. It is important to keep in mind that a severe manic episode and catatonia may co-occur."
Retains the conditional nature of the clinical distinction.
Anti-NMDA receptor encephalitis
Overlapping Features Anti-NMDA receptor encephalitis can cause a full catatonic syndrome or some overlapping signs, including autonomic instability. It is an etiological consideration as well as a diagnostic overlap.
Distinguishing Features
  • A partial or absent lorazepam response does not exclude catatonia associated with anti-NMDA receptor encephalitis.
  • When the cause of catatonia is unclear, the etiological workup may include serum and CSF neuronal autoantibodies.
Show evidence (2 references)
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"This condition may present with full spectrum catatonia, or patients may have only some of the classic symptoms of catatonia, including autonomic instability"
Identifies encephalitis as a potential cause of catatonia, not solely a mimic.
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"incomplete response to a lorazepam challenge test, and some patients with catatonia may not experience a clinical response to lorazepam at all."
Limits the interpretation of a negative challenge test.
Nonconvulsive status epilepticus
Overlapping Features Nonconvulsive status epilepticus may present as catatonia and can be clinically difficult to distinguish.
Distinguishing Features
  • Subtle facial or limb twitching, neurological disease and medication changes affecting seizure threshold increase suspicion.
  • EEG is important when this differential is suspected.
  • Improvement with a lorazepam challenge is not specific because both conditions may respond.
Show evidence (3 references)
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"there is a clear case for an electroencephalogram (EEG) in the context of possible non-convulsive status epilepticus (NCSE), which can present as catatonia"
Supports EEG assessment for this potentially treatable mimic.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"Red flags for NCSE include subtle ictal phenomena (such as twitching of the face or extremities), comorbid neurological disease and a change in medications that affect seizure threshold"
Supplies specific clues to seizure activity.
PMID:37039129 SUPPORT DIRECT REVIEW SYNTHESIS Human Clinical
"stiff person syndrome and NCSE are likely to improve with a lorazepam challenge."
A positive challenge alone cannot distinguish these syndromes.
🔬

Clinical Trials

7
NCT02734498 NOT_APPLICABLE TERMINATED
Study comparing right unilateral and bilateral ECT for catatonia, with a non-ECT comparison group. Recruitment was terminated; this record does not establish the superiority of one electrode placement.
Show evidence (1 reference)
clinicaltrials:NCT02734498 SUPPORT DIRECT BACKGROUND Other
"The purpose of this treatment study is to compare the effectiveness of different electrode placements used in Electroconvulsive Therapy (ECT) in the treatment of catatonia."
The registry summary documents the study objective, not a demonstrated clinical effect.
NCT03116425 NOT_APPLICABLE UNKNOWN
Proof-of-concept study of personalized rTMS targets informed by functional MRI for chronic treatment-resistant catatonia.
Show evidence (1 reference)
clinicaltrials:NCT03116425 SUPPORT DIRECT BACKGROUND Other
"Investigators hypothesize that personalizing rTMS targets using functional MRI will allow to improve symptoms of patients suffering from chronic catatonia."
The registry summary documents the study objective, not a demonstrated clinical effect.
NCT06139432 NOT_APPLICABLE UNKNOWN
CATATOES study evaluating active versus sham tDCS for catatonia.
Show evidence (1 reference)
clinicaltrials:NCT06139432 SUPPORT DIRECT BACKGROUND Other
"Our objective is to evaluate the efficacy of tDCS in catatonia in a clinical trial."
The registry summary documents the study objective, not a demonstrated clinical effect.
NCT06176456 NOT_APPLICABLE UNKNOWN
Placebo-controlled study evaluating the effectiveness and safety of TMS in catatonia.
Show evidence (1 reference)
clinicaltrials:NCT06176456 SUPPORT DIRECT BACKGROUND Other
"Evaluation effectiveness and safety of TMS in subjects with catatonia"
The registry summary documents the study objective, not a demonstrated clinical effect.
NCT06016764 PHASE_I COMPLETED
MRI-targeted continuous theta-burst stimulation study investigating motor-cortex excitability and catatonic symptoms in autism. It is principally a mechanistic probe and does not establish treatment efficacy.
Show evidence (1 reference)
clinicaltrials:NCT06016764 SUPPORT DIRECT BACKGROUND Other
"This application will use a participant's own individual brain magnetic resonance image to target the primary motor strip with transcranial magnetic stimulation; to determine if hyper-excitability of the brain directly correlates with symptoms of catatonia and social-emotional impairment in autism."
The registry summary documents the study objective, not a demonstrated clinical effect.
NCT05662228 PHASE_II COMPLETED
Phase II trial comparing lorazepam, IVIG and tofacitinib in Down syndrome regression disorder, in which catatonia may occur. Its broader regression-disorder population does not establish efficacy of immunotherapy for catatonia generally.
Show evidence (1 reference)
clinicaltrials:NCT05662228 SUPPORT DIRECT BACKGROUND Other
"The study evaluates the safety and efficacy of three currently prescribed therapies: lorazepam, intravenous immunoglobulin (IVIG) and tofacitinib."
The registry summary documents the study objective, not a demonstrated clinical effect.
ISRCTN11236443 PHASE_III RECRUITING
The Laborit study combines an observational cohort with a single-blind randomized comparison of sodium oxybate and continued lorazepam after inadequate initial lorazepam response. The target randomized population has psychiatric-associated catatonia; malignant catatonia and underlying somatic causes are excluded. The protocol is not an efficacy report.
Show evidence (5 references)
PMID:40705436 SUPPORT DIRECT BACKGROUND Human Clinical
"The Laborit trial consists of a cohort study and an embedded single-blind randomized controlled trial (RCT)."
Specifies the study design.
PMID:40705436 SUPPORT DIRECT BACKGROUND Human Clinical
"A total of 42 patients will be randomly assigned to either the sodium oxybate group, after a 2-day lorazepam reduction period, or the continuation of lorazepam."
Planned enrollment and comparator, not actual trial completion.
PMID:40705436 SUPPORT DIRECT PRIMARY RESULT Human Clinical
"As of March 2025, the first 4 participants have been included in the cohort, with no trial participants enrolled yet."
Dated enrollment statement from the protocol publication; not current recruitment status.
+ 2 more references
{ }

Source YAML

click to show 
name: Catatonia
creation_date: '2026-08-14T09:00:00Z'
category: Psychiatric
synonyms:
- catatonic syndrome
- catatonic state
- catatonic disorder
description: >-
  Catatonia is a transdiagnostic psychomotor syndrome affecting movement, speech, affect and
  behavior. It occurs with psychiatric, neurological, neurodevelopmental and general medical
  conditions. Hypokinetic, hyperkinetic and qualitatively abnormal motor signs can overlap or
  fluctuate within an episode. Malignant catatonia includes clinically significant autonomic
  dysfunction and can be life-threatening. Imaging and pharmacological observations implicate
  interacting GABAergic, glutamatergic, dopaminergic and distributed network disturbances, but
  no single mechanism or diagnostic biomarker accounts for all presentations. Benzodiazepines
  and electroconvulsive therapy are first-line treatments; treatment of the underlying condition
  and prevention of medical complications are also required.
disease_term:
  preferred_term: catatonia
  term:
    id: MONDO:0800105
    label: catatonia
parents:
- Mental Health Disorder
- Psychomotor Disorder
classifications:
  harrisons_chapter:
  - classification_value: NEUROLOGIC
mechanistic_hypotheses:
- hypothesis_group_id: distributed_psychomotor_network_model
  hypothesis_label: Distributed psychomotor network model
  status: CANONICAL
  description: >-
    A leading integrative model proposes that heterogeneous upstream conditions disturb interacting
    psychomotor networks. Imaging associations provide candidate circuit locations, but the
    evidence is enriched for schizophrenia-spectrum cohorts and postacute states. Its designation
    as the organizing model does not establish a common causal pathway or a validated biomarker
    across etiologies.
  evidence:
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The best-supported mechanistic model to date comes from neuroimaging
      studies implicating cortico-striatal-thalamic, cortico-cerebellar,
      orbitofrontal, cingulate, and motor-premotor networks.
    explanation: >-
      States the network membership of the canonical model and its evidential
      basis in neuroimaging.
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the evidence supports a convergent model in which diverse upstream
      liabilities destabilize shared psychomotor networks, producing a
      recognizable but heterogeneous syndrome
    explanation: >-
      The convergence claim that justifies modeling catatonia as one entity
      with many entry points rather than as many disease-specific mechanisms.
- hypothesis_group_id: gabaergic_deficit_model
  hypothesis_label: Reduced cortical GABA-A-mediated inhibition in akinetic catatonia
  status: ALTERNATIVE
  description: >-
    Benzodiazepine responses and reduced iomazenil binding motivate a GABAergic hypothesis.
    The small receptor-imaging study identifies altered ligand binding, not a demonstrated receptor
    lesion or direct measurement of inhibitory transmission. GABAergic mechanisms may interact
    with other signaling systems and need not explain every clinical presentation.
  evidence:
  - reference: PMID:10486389
    reference_title: "Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Reduced iomazenil binding suggests decreased density of GABA-A receptors
      in the left sensorimotor cortex in akinetic catatonia.
    explanation: >-
      The authors interpret reduced ligand binding as suggesting lower receptor density; causality
      and functional impairment are not established.
    directness: INDIRECT
    quote_role: PRIMARY_RESULT
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Neurochemical evidence supports the notion of interacting disturbances in
      GABAergic inhibition, glutamatergic/NMDA-mediated excitation, and
      dopaminergic modulation rather than a single-transmitter explanation.
    explanation: >-
      Qualifies the GABA-only account: the contemporary synthesis treats
      GABAergic inhibition as one interacting term, not the whole mechanism.
- hypothesis_group_id: striatal_dopamine_hypofunction_model
  hypothesis_label: Reduced striatal dopaminergic transmission as a transdiagnostic psychomotor substrate
  status: ALTERNATIVE
  description: >-
    Reduced striatal dopamine signaling is proposed as one contributor to the hypokinetic presentation.
    Catatonia-specific imaging evidence is sparse, and evidence from Parkinson disease cannot
    establish an identical mechanism. The review includes single catatonic subjects within PET
    studies and a small longitudinal DAT-SPECT series. CSF homovanillic acid findings are inconsistent,
    including elevation in catatonia; these measurements lack regional and temporal specificity.
    Dopaminergic treatment reports remain preliminary, and the hypothesis does not explain all
    excited or alternating presentations.
  evidence:
  - reference: PMID:40966690
    reference_title: Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Evidence for drug-induced parkinsonism, neuroleptic malignant syndrome, catatonia, obsessional
      slowness and hyperkinetic disorders is less comprehensive and requires further research.
    explanation: >-
      The review explicitly limits the imaging evidence for catatonia.
  - reference: PMID:40966690
    reference_title: Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In catatonia, one study found increased HVA levels relative to healthy controls.
    explanation: >-
      A conflicting biochemical finding prevents treating low CSF dopamine metabolites as an
      established general feature.
  - reference: PMID:40966690
    reference_title: Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      However, the evidence in catatonia and depression remains preliminary with small sample
      sizes and a lack of well-conducted clinical trials.
    explanation: >-
      Qualifies pharmacological support for the proposed mechanism.
- hypothesis_group_id: immune_mediated_model
  hypothesis_label: Immune-mediated NMDA receptor perturbation in autoimmune subgroups
  status: EMERGING
  description: >-
    In a mechanistically distinct subgroup, catatonia arises from autoimmune
    perturbation of glutamatergic signaling — most clearly in NMDA receptor
    antibody encephalitis, where catatonia is present in a majority of reported
    cases. The subgroup matters clinically because its treatment is
    immunotherapy directed at the antibody-mediated process, not only
    benzodiazepines. The arm is EMERGING rather than established as a general
    mechanism because it accounts for a subgroup rather than the syndrome, and
    because peripheral inflammatory biomarkers remain nonspecific.
  evidence:
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Immune mechanisms are particularly relevant in subgroups, especially in
      autoimmune encephalitis and inflammatory CNS conditions, whereas
      peripheral biomarkers remain nonspecific.
    explanation: >-
      Scopes the immune arm to subgroups and records the biomarker limitation
      that keeps it from generalizing.
  - reference: PMID:32070914
    reference_title: "Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Catatonia was present in 60% of these cases.
    explanation: >-
      Quantifies how strongly catatonia tracks with NMDA receptor antibody
      encephalitis in the published case literature.
pathophysiology:
- name: Cortical GABA-A Receptor-Mediated Inhibition Deficit
  biological_scale: MOLECULAR
  description: >-
    Reduced cortical GABA-A-mediated inhibition is a hypothesis motivated by benzodiazepine
    responses and reduced iomazenil binding in a small study of akinetic catatonia. Receptor-ligand
    binding is a proxy for receptor availability, not a direct measure of inhibitory synaptic
    transmission. Matching psychiatric controls for diagnosis and medication strengthens the
    comparison but does not eliminate residual confounding or establish causality.
  locations:
  - preferred_term: sensorimotor cortex
  biological_processes:
  - preferred_term: gamma-aminobutyric acid signaling pathway
    term:
      id: GO:0007214
      label: gamma-aminobutyric acid signaling pathway
    modifier: DECREASED
  evidence:
  - reference: PMID:10486389
    reference_title: "Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Catatonic patients showed significantly lower iomazenil binding and
      altered right-left relations in the left sensorimotor cortex compared with
      psychiatric (p<0.001) and healthy (p<0.001) controls.
    explanation: >-
      A regional binding difference supports the GABAergic hypothesis indirectly; it does not
      directly measure receptor function or exclude all confounding.
    quote_role: PRIMARY_RESULT
    directness: INDIRECT
  - reference: PMID:10486389
    reference_title: "Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Catatonia is a psychomotor syndrome with concomittant akinesia and anxiety
      which both respond almost immediately to benzodiazepines such as lorazepam.
    explanation: >-
      The introduction restates a clinical response that motivated the study; it is not a receptor-restoration
      experiment.
    quote_role: BACKGROUND
    directness: INDIRECT
  downstream:
  - target: Distributed Psychomotor Network Destabilization
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - gabaergic_deficit_model
    - distributed_psychomotor_network_model
    description: >-
      Proposed linkage within the distributed-network model; the intervening causal sequence
      has not been established in catatonia.
  mechanism_confidence: PROVISIONAL
  notes: >-
    The SPECT result concerns a regional signal and does not identify a particular neuronal
    cell type. Needs term: sensorimotor cortex. OLS4 search https://www.ebi.ac.uk/ols4/api/search?q=sensorimotor%20cortex&ontology=uberon&rows=6
    returned supplemental motor cortex (UBERON:0016636) and insular cortex (UBERON:0034891);
    neither denotes the measured sensorimotor region. Primary motor cortex alone is also narrower
    than that region.
- name: Reduced Regional Cortical Perfusion
  biological_scale: TISSUE
  description: >-
    Reduced right lower prefrontal and parietal perfusion was observed in the small akinetic-catatonia
    SPECT study. This regional blood-flow finding is distinct from reduced iomazenil binding
    and does not by itself establish GABA-A receptor dysfunction.
  mechanism_confidence: PROVISIONAL
  evidence:
  - reference: PMID:10486389
    reference_title: 'Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      In addition, there was significantly lower r-CBF in the right lower prefrontal and parietal
      cortex in catatonia
    explanation: >-
      A separate perfusion measurement; its causal relationship to the syndrome remains uncertain.
- name: Reduced Striatal Dopaminergic Transmission
  biological_scale: CELLULAR
  description: >-
    Reduced striatal dopamine signaling is a proposed contributor to hypokinetic catatonia.
    Human imaging observations are sparse and measure presynaptic synthesis, storage or transporter
    availability rather than the complete signaling pathway. The direct/indirect basal-ganglia
    pathway model is mechanistic background; its full sequence has not been demonstrated in
    catatonia. Pharmacological reports and overlap with neuroleptic malignant syndrome support
    investigation but are not a universal explanation.
  locations:
  - preferred_term: striatum
    term:
      id: UBERON:0002435
      label: striatum
  cell_types:
  - preferred_term: dopaminergic neuron
    term:
      id: CL:0000700
      label: dopaminergic neuron
  - preferred_term: medium spiny neuron
    term:
      id: CL:1001474
      label: medium spiny neuron
  biological_processes:
  - preferred_term: dopamine receptor signaling pathway
    term:
      id: GO:0007212
      label: G protein-coupled dopamine receptor signaling pathway
    modifier: DECREASED
  evidence:
  - reference: PMID:40966690
    reference_title: Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Three 18F-FDOPA-PET studies of individuals with psychosis have each included a single
      patient with catatonia
    explanation: >-
      The review describes the very small catatonia-specific PET evidence base.
  - reference: PMID:40966690
    reference_title: Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      five older women with catatonia and depression underwent a DAT-SPECT
    explanation: >-
      The longitudinal transporter-imaging signal comes from a small selected series.
  - reference: PMID:40966690
    reference_title: Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      However, the evidence in catatonia and depression remains preliminary with small sample
      sizes and a lack of well-conducted clinical trials.
    explanation: >-
      The clinical pharmacological evidence is preliminary.
  downstream:
  - target: Distributed Psychomotor Network Destabilization
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - striatal_dopamine_hypofunction_model
    - distributed_psychomotor_network_model
    description: >-
      Proposed linkage within the distributed-network model; the intervening causal sequence
      has not been established in catatonia.
  mechanism_confidence: PROVISIONAL
- name: Autoimmune NMDA Receptor Perturbation
  biological_scale: CELLULAR
  description: >-
    Autoimmune NMDA receptor dysfunction provides one etiological route to catatonia in anti-NMDA
    receptor encephalitis. The downstream circuit sequence generating catatonic signs remains
    uncertain. Published case reports document both hypokinetic and excited signs, sometimes
    in the same patient. This subgroup does not establish microglial activation or a general
    NMDA signaling abnormality in every form of catatonia.
  biological_processes:
  - preferred_term: glutamate receptor signaling pathway
    term:
      id: GO:0007215
      label: glutamate receptor signaling pathway
    modifier: ABNORMAL
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      there is a strong association between anti-NMDA receptor encephalitis and catatonia
    explanation: >-
      Supports the autoimmune etiological subgroup without asserting a measured cell-specific
      signaling change.
  - reference: PMID:42431537
    reference_title: 'Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Immune mechanisms are particularly relevant in subgroups, especially in autoimmune encephalitis
      and inflammatory CNS conditions, whereas peripheral biomarkers remain nonspecific.
    explanation: >-
      Scopes the immune model to selected contexts.
  - reference: PMID:32070914
    reference_title: 'Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      Immobility/stupor and excitement co-occurred in the same patient in 33% of cases.
    explanation: >-
      A systematic review of selected reports documents overlapping signs; it does not identify
      a molecular pathway.
  downstream:
  - target: Distributed Psychomotor Network Destabilization
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - immune_mediated_model
    - distributed_psychomotor_network_model
    description: >-
      Proposed linkage within the distributed-network model; the intervening causal sequence
      has not been established in catatonia.
  mechanism_confidence: PROVISIONAL
- name: Orbitofrontal Emotional-Motor Processing Dysfunction
  biological_scale: TISSUE
  description: >-
    A small emotional-task fMRI study of postacute akinetic catatonia found altered orbitofrontal
    activation and functional connectivity with premotor cortex. Behavioral and affective symptom
    scores correlated with orbitofrontal activity, while motor symptoms were related to medial
    prefrontal activity. A persistent trait abnormality is one interpretation, but postacute
    sampling cannot distinguish predisposition from consequences of illness or treatment.
  locations:
  - preferred_term: orbitofrontal cortex
    term:
      id: UBERON:0004167
      label: orbitofrontal cortex
  - preferred_term: prefrontal cortex
    term:
      id: UBERON:0000451
      label: prefrontal cortex
  evidence:
  - reference: PMID:15279056
    reference_title: "Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Catatonic patients showed alterations in the orbitofrontal cortical
      activation pattern and in functional connectivity to the premotor cortex
      in negative and positive emotions compared to psychiatric and healthy
      controls.
    explanation: >-
      Associational functional imaging localizes a candidate circuit disturbance; it does not
      demonstrate a causal emotional-motor lesion.
    quote_role: PRIMARY_RESULT
    directness: INDIRECT
  - reference: PMID:15279056
    reference_title: "Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Catatonic behavioral and affective symptoms correlated significantly with
      orbitofrontal activity, whereas catatonic motor symptoms were rather
      related to medial prefrontal activity.
    explanation: >-
      Dissociates the affective and motor components onto different prefrontal
      subregions.
    quote_role: PRIMARY_RESULT
    directness: INDIRECT
  - reference: PMID:15279056
    reference_title: "Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Because we investigated postacute patients, orbitofrontal cortical
      alterations may be interpreted as a trait marker predisposing for
      development of catatonic syndrome
    explanation: >-
      The authors' own caveat: post-acute sampling means this may index
      predisposition rather than the acute mechanism.
    quote_role: PRIMARY_RESULT
    directness: INDIRECT
  downstream:
  - target: Distributed Psychomotor Network Destabilization
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - distributed_psychomotor_network_model
    description: >-
      Proposed linkage within the distributed-network model; the intervening causal sequence
      has not been established in catatonia.
  mechanism_confidence: PROVISIONAL
- name: Distributed Psychomotor Network Destabilization
  biological_scale: TISSUE
  description: >-
    A distributed-network model integrates structural and functional imaging associations across
    cortico-striatal-thalamic, cortico-cerebellar, orbitofrontal, cingulate and motor-premotor
    regions. Multimodal MRI in schizophrenia-spectrum participants identifies candidate circuits,
    but does not establish a shared causal substrate across every etiology or catatonic presentation.
    Most neurochemical-to-network links remain mechanistic hypotheses.
  locations:
  - preferred_term: prefrontal cortex
    term:
      id: UBERON:0000451
      label: prefrontal cortex
  - preferred_term: striatum
    term:
      id: UBERON:0002435
      label: striatum
  - preferred_term: thalamus
    term:
      id: UBERON:0001897
      label: dorsal plus ventral thalamus
  - preferred_term: cerebellum
    term:
      id: UBERON:0002037
      label: cerebellum
  - preferred_term: primary motor cortex
    term:
      id: UBERON:0001384
      label: primary motor cortex
  evidence:
  - reference: PMID:31174212
    reference_title: Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      we found predominantly frontothalamic and corticostriatal abnormalities in
      SSD patients with catatonia
    explanation: >-
      Within a schizophrenia-spectrum sample, catatonia is associated with frontothalamic and
      corticostriatal imaging differences; residual confounding and etiological generalizability
      remain unresolved.
    quote_role: PRIMARY_RESULT
  - reference: PMID:31174212
    reference_title: Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      NCRS behavioral scores were associated with a joint structural and
      functional system that predominantly included cerebellar and
      prefrontal/cortical motor regions.
    explanation: >-
      Adds the cerebellar and cortical motor components of the network and ties
      them to symptom severity.
    quote_role: PRIMARY_RESULT
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The best-supported mechanistic model to date comes from neuroimaging
      studies implicating cortico-striatal-thalamic, cortico-cerebellar,
      orbitofrontal, cingulate, and motor-premotor networks.
    explanation: >-
      Establishes this set of networks as the best-supported mechanistic
      account, which is why it is modeled as the hub.
    quote_role: REVIEW_SYNTHESIS
  downstream:
  - target: Hypokinetic Psychomotor Output
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - distributed_psychomotor_network_model
    description: >-
      Proposed linkage within the distributed-network model; the intervening causal sequence
      has not been established in catatonia.
  - target: Hyperkinetic Psychomotor Output
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - distributed_psychomotor_network_model
    description: >-
      Proposed linkage within the distributed-network model; the intervening causal sequence
      has not been established in catatonia.
  - target: Autonomic Decompensation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    hypothesis_groups:
    - distributed_psychomotor_network_model
    description: >-
      Proposed linkage within the distributed-network model; the intervening causal sequence
      has not been established in catatonia.
  - target: Parakinetic Motor Output
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      The distributed-network model proposes that orbitofrontal circuit disturbance can produce
      repetitive and imitative behavior.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        disruptions in the lateral orbitofrontal circuit could produce repetitive and mimicking
        behaviors
      explanation: >-
        A candidate circuit relationship rather than direct causal demonstration.
  mechanism_confidence: PROVISIONAL
- name: Hypokinetic Psychomotor Output
  biological_scale: ORGANISM
  description: >-
    Reduced initiation of movement and speech, including akinesia, stupor and mutism, characterizes
    the hypokinetic presentation. Other motor abnormalities may accompany it, and excited signs
    may occur during the same illness. This clinical pattern is not itself evidence for a unique
    neurotransmitter deficit.
  evidence:
  - reference: PMID:32070914
    reference_title: "Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The phenomenological profile of catatonia in this sample of cases of
      NMDAr-AbE was characterised by a preponderance of signs in the hypokinetic
      spectrum.
    explanation: >-
      Names the hypokinetic spectrum as a distinguishable output and shows it
      predominating in a defined subgroup.
    quote_role: PRIMARY_RESULT
  - reference: PMID:35861966
    reference_title: "Malignant Catatonia: A Review for the Intensivist."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical picture of catatonia ranges from akinetic stupor to severe
      motoric excitement.
    explanation: >-
      Places akinetic stupor at one end of the clinical range this node
      represents.
    quote_role: REVIEW_SYNTHESIS
  downstream:
  - target: Pneumonia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Immobility increases risk of this respiratory complication; the source does not resolve
      the complete intervening pathway.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Patients who are immobile are at risk for respiratory complications (e.g., pulmonary
        embolism, pulmonary atelectasis, pneumonia.
      explanation: >-
        Expert synthesis supports an immobility-related risk, not an inevitable consequence.
  - target: Deep venous thrombosis
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Reported as an increased-risk complication in patients with schizophrenia and catatonic
      stupor. The source does not establish the specific causal intermediates for this complication.
    evidence:
    - reference: PMID:37039129
      reference_title: "Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        increased risk of various infections (pneumonia, urinary tract infection
        and sepsis), disseminated intravascular coagulation, rhabdomyolysis,
        dehydration, deep vein thrombosis, pulmonary embolus, urinary retention,
        decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia
        and liver dysfunction
      explanation: >-
        Cohort evidence that catatonic stupor carries an increased risk of this
        complication.
      quote_role: REVIEW_SYNTHESIS
      directness: INDIRECT
  - target: Pulmonary embolism
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Immobility increases risk of this respiratory complication; the source does not resolve
      the complete intervening pathway.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Patients who are immobile are at risk for respiratory complications (e.g., pulmonary
        embolism, pulmonary atelectasis, pneumonia.
      explanation: >-
        Expert synthesis supports an immobility-related risk, not an inevitable consequence.
  - target: Rhabdomyolysis
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Immobility/stupor and rigidity can increase muscle-complication risk, including rhabdomyolysis;
      patient-level causal intermediates remain unresolved.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Immobility/stupor and rigidity are specific catatonic signs that increase the risk of
        neuromuscular complications (e.g., neuropathies, muscle contractures, deconditioning,
        rhabdomyolysis) and pressure ulcers
      explanation: >-
        Supports a clinical risk relationship without asserting that elevated CK demonstrates
        this route in every patient.
  - target: Pressure ulcer
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Prolonged immobility/stupor increases risk of pressure injury.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Immobility/stupor and rigidity are specific catatonic signs that increase the risk of
        neuromuscular complications (e.g., neuropathies, muscle contractures, deconditioning,
        rhabdomyolysis) and pressure ulcers
      explanation: >-
        Supports the immobility-related pressure-injury complication.
  - target: Mutism
    causal_link_type: DIRECT
    description: >-
      Failure to initiate activity is clinically expressed as this hypokinetic sign.
    evidence:
    - reference: PMID:37039129
      reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: DIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        They concern failures in initiation of activity (stupor, mutism and reduced oral intake)
      explanation: >-
        BAP describes the sign as a manifestation of impaired activity initiation.
  - target: Stupor
    causal_link_type: DIRECT
    description: >-
      Failure to initiate activity is clinically expressed as this hypokinetic sign.
    evidence:
    - reference: PMID:37039129
      reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: DIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        They concern failures in initiation of activity (stupor, mutism and reduced oral intake)
      explanation: >-
        BAP describes the sign as a manifestation of impaired activity initiation.
  - target: Reduced Oral Intake
    causal_link_type: DIRECT
    description: >-
      Reduced initiation and withdrawal can impair eating and drinking.
    evidence:
    - reference: PMID:37039129
      reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: DIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        They concern failures in initiation of activity (stupor, mutism and reduced oral intake)
      explanation: >-
        Clinical-level link from reduced initiation to intake impairment.
  - target: Akinesia
    causal_link_type: DIRECT
    description: >-
      Absent voluntary movement is a clinical expression of the hypokinetic dimension.
    evidence:
    - reference: PMID:35861966
      reference_title: "Malignant Catatonia: A Review for the Intensivist."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The clinical picture of catatonia ranges from akinetic stupor to severe
        motoric excitement.
      explanation: >-
        The review places akinetic stupor at the reduced-movement end of the clinical spectrum;
        this is a clinical manifestation link, not an established molecular mechanism.
      quote_role: REVIEW_SYNTHESIS
      directness: DIRECT
- name: Hyperkinetic Psychomotor Output
  biological_scale: ORGANISM
  description: >-
    Increased, non-purposeful motor activity is the hyperkinetic dimension of catatonia. It
    may fluctuate with hypokinetic signs within an episode. This dimension is distinct from
    qualitative abnormalities of movement, although both may coexist.
  evidence:
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      catatonia is internally heterogeneous, with hypokinetic, hyperkinetic, and
      aberrant-volitional components that often overlap within the same episode
    explanation: >-
      The review distinguishes hyperkinetic from aberrant-volitional components while allowing
      overlap.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:32070914
    reference_title: "Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      However, excitement often co-occurred in these patients suggesting that
      fluctuations in catatonic semiology may be frequent.
    explanation: >-
      Empirical support for within-episode fluctuation between the two poles.
    quote_role: PRIMARY_RESULT
  downstream:
  - target: Agitation
    causal_link_type: DIRECT
    description: >-
      Non-goal-directed agitation is a manifestation of the increased-motor-activity dimension.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: DIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        In hyperkinetic catatonia, there are often non-purposeful and abrupt states of psychomotor
        agitation that may resemble akathisia.
      explanation: >-
        Links the motor dimension to agitation at the clinical level.
- name: Parakinetic Motor Output
  biological_scale: ORGANISM
  mechanism_confidence: PROVISIONAL
  description: >-
    Qualitatively abnormal, context-inappropriate motor behavior is the parakinetic dimension
    of catatonia. A proposed lateral orbitofrontal circuit disturbance could contribute to repetitive
    or imitative behaviors. The circuit explanation is provisional and these signs need not
    imply increased overall motor activity.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Catatonia can present as hypokinetic (reduced activity), hyperkinetic (elevated activity),
      or parakinetic (odd, purposeless motor behaviors unrelated to amount of motor activity)
    explanation: >-
      Distinguishes the qualitative motor dimension from overall activity.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: INDIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      disruptions in the lateral orbitofrontal circuit could produce repetitive and mimicking
      behaviors
    explanation: >-
      Proposed circuit-to-behavior relationship, not a demonstrated universal mechanism.
  downstream:
  - target: Motor stereotypy
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Repetitive or imitative movement is a clinical expression of the proposed abnormal motor-output
      process.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        disruptions in the lateral orbitofrontal circuit could produce repetitive and mimicking
        behaviors
      explanation: >-
        The model proposes a route to this behavior; intermediate causal events have not been
        established.
  - target: Echopraxia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Repetitive or imitative movement is a clinical expression of the proposed abnormal motor-output
      process.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        disruptions in the lateral orbitofrontal circuit could produce repetitive and mimicking
        behaviors
      explanation: >-
        The model proposes a route to this behavior; intermediate causal events have not been
        established.
  - target: Echolalia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      Imitative speech is a clinical expression of the proposed abnormal motor-output process.
      The circuit explanation remains provisional.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        disruptions in the lateral orbitofrontal circuit could produce repetitive and mimicking
        behaviors
      explanation: >-
        The proposed circuit account includes mimicking behaviors; echolalia is the speech manifestation,
        without proof of a universal circuit lesion.
    - reference: PMID:37236789
      reference_title: The diagnosis and treatment of catatonia.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Echolalia (repetition of another person's speech)
      explanation: >-
        The DSM-5-TR criterion definition for echolalia as a catatonic sign.
      quote_role: REVIEW_SYNTHESIS
- name: Autonomic Decompensation
  biological_scale: ORGANISM
  description: >-
    Clinically significant autonomic abnormalities define malignant catatonia. Hyperthermia,
    tachycardia and blood-pressure abnormalities may accompany any motor presentation. The condition
    is life-threatening and overlaps clinically with neuroleptic malignant syndrome; the relationship
    between the two syndromes remains debated.
  evidence:
  - reference: PMID:35861966
    reference_title: "Malignant Catatonia: A Review for the Intensivist."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Malignant catatonia describes catatonia that presents with clinically
      significant autonomic abnormalities including change in temperature, blood
      pressure, heart rate, and respiratory rate.
    explanation: >-
      Defines the autonomic decompensation this node represents.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:35861966
    reference_title: "Malignant Catatonia: A Review for the Intensivist."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Prompt recognition and treatment of catatonia are crucial because malignant
      catatonia may be fatal without treatment.
    explanation: >-
      Records the outcome that makes this node the highest-stakes branch of the
      graph.
    quote_role: REVIEW_SYNTHESIS
  downstream:
  - target: Fever
    causal_link_type: DIRECT
    description: >-
      Clinically significant autonomic dysfunction in malignant catatonia can manifest as this
      sign.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: DIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Malignant catatonia is a life-threatening subtype of catatonia with symptoms of altered
        level of arousal, rigidity, autonomic instability (e.g., hyperthermia, tachycardia)
      explanation: >-
        Names the direction-specific autonomic manifestations.
  - target: Tachycardia
    causal_link_type: DIRECT
    description: >-
      Clinically significant autonomic dysfunction in malignant catatonia can manifest as this
      sign.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: DIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Malignant catatonia is a life-threatening subtype of catatonia with symptoms of altered
        level of arousal, rigidity, autonomic instability (e.g., hyperthermia, tachycardia)
      explanation: >-
        Names the direction-specific autonomic manifestations.
- name: Reduced Oral Intake
  biological_scale: ORGANISM
  description: >-
    Catatonic withdrawal and impaired initiation of activity may reduce eating and drinking,
    producing nutritional and fluid deficits.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Nutritional deficiencies may occur due to the catatonic feature of withdrawal leading
      to poor oral intake.
    explanation: >-
      Specifies an intermediate between withdrawal and nutritional complications.
  downstream:
  - target: Malnutrition
    causal_link_type: DIRECT
    description: >-
      Insufficient intake can produce nutritional deficiency.
    evidence:
    - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: DIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Nutritional deficiencies may occur due to the catatonic feature of withdrawal leading
        to poor oral intake.
      explanation: >-
        The document explicitly attributes nutritional deficiency to poor intake.
phenotypes:
- category: Behavioral
  name: Mutism
  description: >-
    Absence of, or dramatic reduction in, speech. One of the two most prevalent
    signs in the NMDA receptor antibody encephalitis case literature and a core
    diagnostic criterion.
  phenotype_term:
    preferred_term: Mutism
    term:
      id: HP:0002300
      label: Mutism
  evidence:
  - reference: PMID:32070914
    reference_title: "Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most prevalent signs were immobility/stupor (70%), mutism (67%),
      excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and
      rigidity (30%).
    explanation: >-
      Quantifies mutism among the most prevalent catatonic signs in a defined
      cohort.
    quote_role: PRIMARY_RESULT
- category: Motor
  name: Akinesia
  description: >-
    Reduction or absence of spontaneous movement, up to akinetic stupor. The
    akinetic presentation is the one in which the GABA-A receptor imaging
    findings were obtained.
  phenotype_term:
    preferred_term: Akinesia
    term:
      id: HP:0002304
      label: Akinesia
  evidence:
  - reference: PMID:35861966
    reference_title: "Malignant Catatonia: A Review for the Intensivist."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical picture of catatonia ranges from akinetic stupor to severe
      motoric excitement.
    explanation: >-
      Establishes akinetic stupor as a recognized presentation of catatonia.
    quote_role: REVIEW_SYNTHESIS
- category: Motor
  name: Abnormal posturing
  description: >-
    Spontaneous assumption of a posture maintained against gravity, distinct from the examiner-induced
    posture of catalepsy.
  phenotype_term:
    preferred_term: Abnormal posturing
    term:
      id: HP:0002533
      label: Abnormal posturing
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Posturing (spontaneous assumption of postures sustained against gravity)
    explanation: >-
      Defines active posturing as a distinct catatonic sign.
- category: Motor
  name: Motor stereotypy
  description: >-
    Non-goal-directed movement repeated at abnormal frequency. This qualitative motor sign can
    occur with either reduced or increased overall activity.
  phenotype_term:
    preferred_term: Motor stereotypy
    term:
      id: HP:0000733
      label: Motor stereotypy
  evidence:
  - reference: PMID:32070914
    reference_title: "Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most prevalent signs were immobility/stupor (70%), mutism (67%),
      excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and
      rigidity (30%).
    explanation: >-
      Reports stereotypies among the ascertained catatonic signs.
    quote_role: PRIMARY_RESULT
- category: Motor
  name: Rigidity
  description: >-
    Increased muscle tone on passive movement, distinct from the waxy
    flexibility in which resistance to repositioning is steady and even.
  phenotype_term:
    preferred_term: Rigidity
    term:
      id: HP:0002063
      label: Rigidity
  evidence:
  - reference: PMID:32070914
    reference_title: "Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most prevalent signs were immobility/stupor (70%), mutism (67%),
      excitement (50%), posturing/catalepsy (34%), stereotypies (31%), and
      rigidity (30%).
    explanation: >-
      Reports rigidity among the ascertained catatonic signs.
    quote_role: PRIMARY_RESULT
- category: Behavioral
  name: Negativism
  description: >-
    Resistance to instructions, which may extend to doing the opposite of what
    is asked — an aberrant-volitional rather than purely motor sign.
  phenotype_term:
    preferred_term: Negativism
    term:
      id: HP:0410291
      label: Negativism
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Negativism (resistance to instructions, which might even entail doing the
      opposite to them)
    explanation: >-
      The DSM-5-TR criterion definition, from the BAP concise guideline's
      summary of diagnostic criteria.
    quote_role: REVIEW_SYNTHESIS
- category: Behavioral
  name: Echolalia
  description: >-
    Repetition of another person's speech; with echopraxia (mimicry of another
    person's movements) these constitute the echophenomena of catatonia.
  phenotype_term:
    preferred_term: Echolalia
    term:
      id: HP:0010529
      label: Echolalia
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Echolalia (repetition of another person's speech)
    explanation: >-
      The DSM-5-TR criterion definition for echolalia as a catatonic sign.
    quote_role: REVIEW_SYNTHESIS
- category: Behavioral
  name: Facial grimacing
  description: >-
    Grimacing is a listed diagnostic feature and, in periodic catatonia, a
    characteristic long-term residual sign.
  phenotype_term:
    preferred_term: Facial grimacing
    term:
      id: HP:0000273
      label: Facial grimacing
  evidence:
  - reference: PMID:12384773
    reference_title: "Periodic catatonia: confirmation of linkage to chromosome 15 and further evidence for genetic heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The disorder is characterized by qualitative hyperkinetic and akinetic
      psychomotor disturbances through acute psychotic episodes and debilitating
      symptoms in the long term, with psychomotor weakness, grimacing facial
      movements and apathy.
    explanation: >-
      Reports grimacing facial movements as a persistent feature in the
      periodic-catatonia phenotype.
    quote_role: PRIMARY_RESULT
- category: Behavioral
  name: Agitation
  description: >-
    Agitation that is not prompted by external stimuli, part of the excited
    presentation.
  phenotype_term:
    preferred_term: Agitation
    term:
      id: HP:0000713
      label: Agitation
  evidence:
  - reference: PMID:35861966
    reference_title: "Malignant Catatonia: A Review for the Intensivist."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical picture of catatonia ranges from akinetic stupor to severe
      motoric excitement.
    explanation: >-
      Establishes severe motoric excitement as a recognized pole of the
      syndrome.
    quote_role: REVIEW_SYNTHESIS
- category: Autonomic
  name: Fever
  description: >-
    Hyperthermia can accompany malignant catatonia.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In some cases, this can lead to a life-threatening elevation in blood pressure, heart
      rate and body temperature with a poor outcome.
    explanation: >-
      The malignant-catatonia definition states the direction of change, not only an unspecified
      autonomic disturbance.
- category: Autonomic
  name: Tachycardia
  description: >-
    An elevated heart rate can accompany malignant catatonia.
  phenotype_term:
    preferred_term: Tachycardia
    term:
      id: HP:0001649
      label: Tachycardia
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In some cases, this can lead to a life-threatening elevation in blood pressure, heart
      rate and body temperature with a poor outcome.
    explanation: >-
      The malignant-catatonia definition states the direction of change, not only an unspecified
      autonomic disturbance.
- category: Respiratory
  name: Pneumonia
  description: >-
    Pneumonia is reported among the complications associated with catatonic stupor in a schizophrenia
    cohort summarized by the guideline. This association does not identify a specific causal
    pathway in every patient.
  phenotype_term:
    preferred_term: Pneumonia
    term:
      id: HP:0002090
      label: Pneumonia
  evidence:
  - reference: PMID:37039129
    reference_title: "Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection
      and sepsis), disseminated intravascular coagulation, rhabdomyolysis,
      dehydration, deep vein thrombosis, pulmonary embolus, urinary retention,
      decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia
      and liver dysfunction
    explanation: >-
      Names pneumonia among the complications carried by catatonic stupor in the
      cited cohort.
    quote_role: REVIEW_SYNTHESIS
- category: Cardiovascular
  name: Deep venous thrombosis
  description: >-
    Deep venous thrombosis is reported among the complications associated with catatonic stupor
    in a schizophrenia cohort summarized by the guideline. This association does not identify
    a specific causal pathway in every patient.
  phenotype_term:
    preferred_term: Deep venous thrombosis
    term:
      id: HP:0002625
      label: Deep venous thrombosis
  evidence:
  - reference: PMID:37039129
    reference_title: "Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection
      and sepsis), disseminated intravascular coagulation, rhabdomyolysis,
      dehydration, deep vein thrombosis, pulmonary embolus, urinary retention,
      decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia
      and liver dysfunction
    explanation: >-
      Lists deep vein thrombosis among the complications of catatonic stupor.
    quote_role: REVIEW_SYNTHESIS
- category: Cardiovascular
  name: Pulmonary embolism
  description: >-
    Pulmonary embolism is reported among the complications associated with catatonic stupor
    in a schizophrenia cohort summarized by the guideline. This association does not identify
    a specific causal pathway in every patient.
  phenotype_term:
    preferred_term: Pulmonary embolism
    term:
      id: HP:0002204
      label: Pulmonary embolism
  evidence:
  - reference: PMID:37039129
    reference_title: "Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection
      and sepsis), disseminated intravascular coagulation, rhabdomyolysis,
      dehydration, deep vein thrombosis, pulmonary embolus, urinary retention,
      decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia
      and liver dysfunction
    explanation: >-
      Lists pulmonary embolus among the complications of catatonic stupor.
    quote_role: REVIEW_SYNTHESIS
- category: Musculoskeletal
  name: Rhabdomyolysis
  description: >-
    Rhabdomyolysis is reported among the complications associated with catatonic stupor in a
    schizophrenia cohort summarized by the guideline. This association does not identify a specific
    causal pathway in every patient.
  phenotype_term:
    preferred_term: Rhabdomyolysis
    term:
      id: HP:0003201
      label: Rhabdomyolysis
  evidence:
  - reference: PMID:37039129
    reference_title: "Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection
      and sepsis), disseminated intravascular coagulation, rhabdomyolysis,
      dehydration, deep vein thrombosis, pulmonary embolus, urinary retention,
      decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia
      and liver dysfunction
    explanation: >-
      Lists rhabdomyolysis among the complications of catatonic stupor.
    quote_role: REVIEW_SYNTHESIS
- category: Hematologic
  name: Disseminated intravascular coagulation
  description: >-
    Disseminated intravascular coagulation has been reported at increased frequency in patients
    with catatonic stupor. This cohort association does not establish a causal route from hypokinetic
    output or autonomic decompensation.
  phenotype_term:
    preferred_term: Disseminated intravascular coagulation
    term:
      id: HP:0005521
      label: Disseminated intravascular coagulation
  evidence:
  - reference: PMID:37039129
    reference_title: "Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection
      and sepsis), disseminated intravascular coagulation, rhabdomyolysis,
      dehydration, deep vein thrombosis, pulmonary embolus, urinary retention,
      decubitus ulcers, cardiac arrhythmia, renal failure, NMS, hypernatraemia
      and liver dysfunction
    explanation: >-
      Lists disseminated intravascular coagulation among the complications of
      catatonic stupor.
    quote_role: REVIEW_SYNTHESIS
- name: Stupor
  category: Behavioral
  description: >-
    Lack of responsiveness to the environment; apparent unresponsiveness does not establish
    coma.
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Stupor (lack of responsiveness to the environment)
    explanation: >-
      Listed among DSM-5-TR catatonic signs in the concise guideline.
  phenotype_term:
    preferred_term: Stupor
  notes: >-
    Needs term: OLS4 HP search on 2026-10-04 for 'stupor' returned coma and akinetic mutism,
    which are not equivalent to catatonic stupor. Search endpoint: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=stupor.
    The descriptor is retained without a misleading ontology equivalence.
- name: Catalepsy
  category: Motor
  description: >-
    Maintenance against gravity of a posture induced by an examiner.
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Catalepsy (a posture induced by an external agent is sustained against gravity)
    explanation: >-
      Listed among DSM-5-TR catatonic signs in the concise guideline.
  phenotype_term:
    preferred_term: Catalepsy
  notes: >-
    Needs term: OLS4 HP search on 2026-10-04 for 'catalepsy' returned no hits. Search endpoint:
    https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=catalepsy. The descriptor is retained
    without a misleading ontology equivalence.
- name: Waxy flexibility
  category: Motor
  description: >-
    Steady, even resistance when the examiner repositions a limb.
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Waxy flexibility (steady, even resistance to repositioning)
    explanation: >-
      Listed among DSM-5-TR catatonic signs in the concise guideline.
  phenotype_term:
    preferred_term: Waxy flexibility
  notes: >-
    Needs term: OLS4 HP search on 2026-10-04 for 'waxy flexibility' returned no hits. Search
    endpoint: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=waxy%20flexibility. The descriptor
    is retained without a misleading ontology equivalence.
- name: Mannerism
  category: Motor
  description: >-
    An exaggerated or caricatured normal motor act.
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Mannerism (caricature of a normal motor act)
    explanation: >-
      Listed among DSM-5-TR catatonic signs in the concise guideline.
  phenotype_term:
    preferred_term: Mannerism
  notes: >-
    Needs term: OLS4 HP search on 2026-10-04 for 'mannerism' returned motor stereotypy and broader
    behavior terms, none equivalent to a caricature of a normal motor act. Search endpoint:
    https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=mannerism. The descriptor is retained
    without a misleading ontology equivalence.
- name: Echopraxia
  category: Behavioral
  description: >-
    Mimicry of another person's movements.
  evidence:
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Echopraxia (mimicry of another person's movements)
    explanation: >-
      Listed among DSM-5-TR catatonic signs in the concise guideline.
  phenotype_term:
    preferred_term: Echopraxia
    term:
      id: HP:0020124
      label: Echopraxia
- name: Pressure ulcer
  category: Integument
  description: >-
    A medical complication reported in association with catatonic stupor, warranting clinical
    assessment and prevention where possible.
  phenotype_term:
    preferred_term: Pressure ulcer
    term:
      id: HP:0012399
      label: Pressure ulcer
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection and sepsis),
      disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis,
      pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure,
      NMS, hypernatraemia and liver dysfunction
    explanation: >-
      The guideline names decubitus ulcers among complications observed in the cited clinical
      cohort.
- name: Dehydration
  category: Metabolic
  description: >-
    A medical complication reported in association with catatonic stupor, warranting clinical
    assessment and prevention where possible.
  phenotype_term:
    preferred_term: Dehydration
    term:
      id: HP:0001944
      label: Dehydration
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection and sepsis),
      disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis,
      pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure,
      NMS, hypernatraemia and liver dysfunction
    explanation: >-
      The guideline names dehydration among complications observed in the cited clinical cohort.
- name: Urinary retention
  category: Genitourinary
  description: >-
    A medical complication reported in association with catatonic stupor, warranting clinical
    assessment and prevention where possible.
  phenotype_term:
    preferred_term: Urinary retention
    term:
      id: HP:0000016
      label: Urinary retention
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      increased risk of various infections (pneumonia, urinary tract infection and sepsis),
      disseminated intravascular coagulation, rhabdomyolysis, dehydration, deep vein thrombosis,
      pulmonary embolus, urinary retention, decubitus ulcers, cardiac arrhythmia, renal failure,
      NMS, hypernatraemia and liver dysfunction
    explanation: >-
      The guideline names urinary retention among complications observed in the cited clinical
      cohort.
- name: Malnutrition
  category: Metabolic
  description: >-
    Nutritional deficiency may develop when catatonic withdrawal reduces oral intake. This is
    a complication requiring monitoring and nutritional support, not a mandatory diagnostic
    feature.
  phenotype_term:
    preferred_term: Malnutrition
    term:
      id: HP:0004395
      label: Malnutrition
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Nutritional deficiencies may occur due to the catatonic feature of withdrawal leading
      to poor oral intake.
    explanation: >-
      Supports the nutritional complication and its clinical route.
genetic:
- name: Chromosome 15q15 periodic catatonia susceptibility locus
  presence: Linkage confirmed in a subset of multiplex families
  relationship_type: SUSCEPTIBILITY
  association: >-
    Periodic catatonia, a familial sub-phenotype with recurrent hyperkinetic and akinetic psychomotor
    episodes, maps to a major susceptibility locus on chromosome 15q15, confirmed in a second
    independent genome scan. The linkage study did not identify a causal gene, and it demonstrated
    genetic heterogeneity between families, so this is recorded as a susceptibility locus rather
    than as a catatonia gene.
  evidence:
  - reference: PMID:12384773
    reference_title: "Periodic catatonia: confirmation of linkage to chromosome 15 and further evidence for genetic heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Here, we confirm mapping of a major gene locus on chromosome 15q15 in a
      second genome scan in a new set of four multiplex families.
    explanation: >-
      Independent confirmation of the linkage signal in a new family set.
  - reference: PMID:12384773
    reference_title: "Periodic catatonia: confirmation of linkage to chromosome 15 and further evidence for genetic heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Analysis of individual families showed that one large family showed
      linkage, whereas two others could be clearly excluded, confirming genetic
      heterogeneity.
    explanation: >-
      The heterogeneity caveat: the locus explains some families and is
      excluded in others, so it cannot be read as a general catatonia gene.
  notes: >-
    Historical linkage evidence in multiplex families selected for periodic catatonia. The cited
    study reports locus heterogeneity and does not establish a causal gene or a genetic test
    for catatonia as a whole.
prevalence:
- population: Clinical samples worldwide (psychiatric and medical settings)
  measure_type: UNKNOWN
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 9000.0
  rate_low: 6900.0
  rate_high: 11700.0
  notes: >-
    Pooled clinical-sample proportion of 9.0% (95% CI 6.9-11.7%; I2 = 98%) across heterogeneous
    psychiatric and medical settings. The underlying studies have differing designs and ascertainment
    windows, so a common point-prevalence time frame is not assigned. This is not a general-population
    estimate. The abstract and main tables disagree slightly on total sample size; no combined
    denominator is inferred.
  evidence:
  - reference: PMID:29140521
    reference_title: "Prevalence of Catatonia and Its Moderators in Clinical Samples: Results from a Meta-analysis and Meta-regression Analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      mean catatonia prevalence was 9.0% (k = 80, n = 110764; 95% CI = 6.9-11.7,
      I2 = 98%, publication bias P < .01)
    explanation: >-
      The pooled meta-analytic estimate, quoted with its confidence interval and
      heterogeneity statistic.
    quote_role: PRIMARY_RESULT
- population: South London and Maudsley catchment population, London, UK, 2007-2016; clinician-diagnosed catatonia
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 10.6
  rate_low: 10.0
  rate_high: 11.1
  rate_denominator: PERSON_YEARS
  notes: >-
    Counts new episodes, including recurrent episodes in the same person. Ascertainment required
    a clinical diagnosis and documented catatonic features; retrospective recognition and referral
    to psychiatric services affect capture. This local estimate is not worldwide incidence and
    uses a broader case definition than the later DSM-5-TR reanalysis.
  evidence:
  - reference: PMID:35135642
    reference_title: 'Catatonia: demographic, clinical and laboratory associations.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      giving an incidence of 10.6 (95% CI 10.0–11.1) episodes per 100 000 person-years.
    explanation: >-
      The full results identify the catchment-specific episode rate and confidence interval.
- population: South London and Maudsley catchment population, London, UK, 2007-2016; DSM-5-TR reanalysis
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BAND_1_9_PER_100000
  rate_per_100000: 4.34
  rate_low: 3.98
  rate_high: 4.72
  rate_denominator: PERSON_YEARS
  notes: >-
    Reanalysis of the same London data using DSM-5-TR criteria, counting each new episode separately,
    including recurrences. This is not an independent cohort or a first-onset incidence rate.
  evidence:
  - reference: PMID:39789943
    reference_title: The Population-Based Incidence and Prevalence of Catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      This represents an incidence of 4.34 (95% CI 3.98 to 4.72) catatonic episodes per 100,000
      person-years.
    explanation: >-
      The primary reanalysis provides a stricter case-definition estimate.
- population: Individuals with autism spectrum disorder in heterogeneous research samples
  measure_type: UNKNOWN
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 10400.0
  rate_low: 5800.0
  rate_high: 18000.0
  notes: >-
    Pooled proportion across seven nonoverlapping samples comprising 969 individuals, with substantial
    heterogeneity and mixed cross-sectional and longitudinal designs. The shared measure is
    not a population point prevalence. Catatonia requires a new onset or marked worsening of
    symptoms relative to the individual autistic baseline.
  evidence:
  - reference: PMID:34906264
    reference_title: "Catatonia in autism spectrum disorders: A systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Our meta-analysis showed that 10.4% (5.8-18.0 95%CI) of individuals with
      ASD have catatonia.
    explanation: >-
      The systematic review computes a pooled proportion from selected ASD research samples;
      it does not estimate a worldwide population rate.
    quote_role: PRIMARY_RESULT
- population: Published NMDA receptor antibody encephalitis case reports
  measure_type: UNKNOWN
  prevalence_class: ABOVE_1_IN_1000
  rate_per_100000: 60000.0
  notes: >-
    The review retrospectively applied a two-core-sign screening threshold to 189 individuals
    in 139 published reports. Its 60% proportion describes selected case literature, with ascertainment
    and publication bias; it is neither population prevalence nor a defensible upper bound on
    that prevalence.
  evidence:
  - reference: PMID:32070914
    reference_title: "Catatonia in N-methyl-d-aspartate receptor antibody encephalitis: Phenomenological characteristics from a systematic review of case reports."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: Catatonia was present in 60% of these cases.
    explanation: >-
      The proportion of NMDA receptor antibody encephalitis cases meeting
      catatonia criteria in this systematic review.
    quote_role: PRIMARY_RESULT
diagnosis:
- name: Clinical assessment and diagnostic criteria
  description: >-
    Diagnosis is clinical, requiring three or more catatonic signs under DSM-5-TR or ICD-11.
    DSM-5-TR lists stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerism,
    stereotypy, agitation, grimacing, echolalia and echopraxia. Observation, elicitation and
    physical examination are complementary, and collateral history helps identify fluctuating
    signs and underlying conditions. In autism, a marked change from baseline is required.
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Catatonia should be diagnosed based on the presence of three or more catatonic signs,
      as in DSM-5-TR or ICD-11.
    explanation: >-
      The guideline recommends a clinical sign threshold; a response to medication is not required.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Diagnosis of catatonia in autism spectrum disorder requires a marked change from baseline
      presentation.
    explanation: >-
      Distinguishes a new catatonic syndrome from overlapping baseline autistic features.
- name: Bush-Francis Catatonia Rating Scale
  description: >-
    The BFCRS is a widely used instrument for screening and quantifying catatonic signs and
    tracking treatment response. Its first 14 items form the screening instrument; the full
    scale has 23 items. Scale findings should be translated into diagnostic criteria, since
    definitions of motor signs differ between instruments.
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The first 14 items of the BFCRS comprise the Bush-Francis Catatonia Screening Instrument
      (BFCSI).
    explanation: >-
      Defines the screening subset.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The full 23-item scale evaluates all ICD-11 catatonia criteria.
    explanation: >-
      Defines the full scale coverage.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The results of a catatonia rating scale should be converted to diagnostic criteria for
      clinical diagnosis
    explanation: >-
      Scale thresholds and formal diagnostic criteria are not interchangeable.
  - reference: PMID:8686484
    reference_title: Catatonia. II. Treatment with lorazepam and electroconvulsive therapy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      The rating scale has predictive value and displays sensitivity to change in clinical status.
    explanation: >-
      The prospective treatment study supports using the scale to monitor change.
- name: Lorazepam challenge test
  description: >-
    A lorazepam challenge can support an uncertain diagnosis and help predict benzodiazepine
    response. A reduction in catatonic signs supports catatonia but is not fully specific: nonconvulsive
    status epilepticus and stiff-person syndrome may also improve. A negative response does
    not by itself establish another diagnosis.
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      A positive response to a lorazepam challenge, commonly defined as a 50% reduction in catatonic
      signs on a standardised scale, makes a diagnosis of catatonia more likely, but it is not
      100% specific.
    explanation: >-
      The guideline supplies an operational response threshold and its specificity limit.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Challenge tests are useful in many situations
    explanation: >-
      The challenge supplements clinical assessment.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      stiff person syndrome and NCSE are likely to improve with a lorazepam challenge.
    explanation: >-
      Benzodiazepine responsiveness also occurs in important mimics.
  - reference: PMID:8686484
    reference_title: Catatonia. II. Treatment with lorazepam and electroconvulsive therapy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      A positive response to an initial parenteral challenge predicted final lorazepam response,
      as did length of catatonic symptoms prior to treatment.
    explanation: >-
      Predictive association in an open prospective treatment protocol.
- name: Investigation of underlying conditions and mimics
  description: >-
    Investigations are selected according to history, examination, severity and suspected causes.
    A first or unexplained episode warrants consideration of brain CT or MRI and serum and CSF
    neuronal autoantibodies, including NMDA receptor antibodies. EEG is considered where seizures,
    encephalitis or nonconvulsive status epilepticus are suspected. These tests investigate
    causes and mimics; none is a general diagnostic biomarker for catatonia.
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In patients experiencing a first episode of catatonia or where the diagnosis underlying
      catatonia is unclear, consider a CT or MRI scan of the brain.
    explanation: >-
      Neuroimaging is part of etiological evaluation rather than a confirmatory catatonia test.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In patients experiencing a first episode of catatonia or where the diagnosis underlying
      catatonia is unclear, consider assessing for the presence of antibodies to the NMDA receptor
      and other relevant autoantibodies in serum and CSF.
    explanation: >-
      Supports testing for autoimmune causes when the presentation warrants investigation.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In patients with risk factors for seizures, possible evidence of a seizure or possible
      encephalitis, consider performing an EEG (with continuous monitoring if available).
    explanation: >-
      Scopes EEG to clinical indications.
- name: Assessment of medical complications
  description: >-
    Physical assessment includes hydration, nutritional intake, temperature and other vital
    signs, pressure areas, and signs of venous thrombosis. Laboratory investigations and monitoring
    are guided by suspected complications. Reduced responsiveness should not be assumed to mean
    absent awareness or deliberate refusal of care.
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Physical examination should include assessment for catatonic signs, signs of medical conditions
      that may have led to the catatonia and signs of medical complications of catatonia.
    explanation: >-
      Medical examination addresses both causes and consequences.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      When assessing a patient with catatonia, clinicians should interact with the person as
      if they are able to understand what is being said to them.
    explanation: >-
      Impaired motor or verbal output does not establish absent comprehension.
treatments:
- name: Lorazepam
  description: >-
    Lorazepam is a positive allosteric modulator of GABA-A receptors and a first-line treatment
    for catatonia. In an open prospective study, signs resolved in 16 of 21 patients completing
    a lorazepam trial; this is an uncontrolled response proportion. Treatment is titrated to
    clinical response and tolerability, with attention to sedation and respiratory effects.
    Benzodiazepines are tapered rather than stopped abruptly because withdrawal can precipitate
    recurrence. Response varies with clinical context and may be less reliable in chronic catatonia
    associated with schizophrenia. When catatonia follows benzodiazepine withdrawal, a benzodiazepine
    can be reinstated. Older adults may respond to lower doses.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: lorazepam
      term:
        id: CHEBI:6539
        label: Lorazepam
  target_mechanisms:
  - target: Cortical GABA-A Receptor-Mediated Inhibition Deficit
    treatment_effect: MODULATES
    description: >-
      Lorazepam enhances GABA-A receptor signaling. Its clinical efficacy is compatible with
      a GABAergic contribution to catatonia but does not demonstrate restoration of receptor
      density or establish a universal inhibitory deficit.
    evidence:
    - reference: PMID:37039129
      reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      directness: INDIRECT
      quote_role: REVIEW_SYNTHESIS
      snippet: >-
        Lorazepam is a non-selective positive allosteric modulator of GABA-A receptors.
      explanation: >-
        The drug action is established; its linkage to the proposed disease deficit is indirect.
  evidence:
  - reference: PMID:8686484
    reference_title: "Catatonia. II. Treatment with lorazepam and electroconvulsive therapy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In 16 of 21 patients (76%) who received a complete trial of lorazepam (11
      with initial intravenous challenge), catatonic signs resolved.
    explanation: >-
      The prospective, quantitatively monitored response rate underpinning
      first-line status.
    quote_role: PRIMARY_RESULT
  - reference: PMID:37236789
    reference_title: The diagnosis and treatment of catatonia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      First-line treatment comprises benzodiazepines and/or electroconvulsive
      therapy. The benzodiazepine of choice is lorazepam, which is sometimes
      used in very high doses.
    explanation: >-
      Current guideline statement of first-line status and the drug of choice.
    quote_role: REVIEW_SYNTHESIS
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Benzodiazepines for catatonia should not be stopped abruptly but rather tapered down.
    explanation: >-
      Addresses withdrawal and recurrence risk.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where lorazepam is used for catatonia, high doses above the licensed maximum may be necessary
      to achieve maximal effect.
    explanation: >-
      The guideline permits specialist titration; a high dose is not required when symptoms
      resolve or side effects limit treatment.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where catatonia has resulted from benzodiazepine withdrawal, restart a benzodiazepine.
    explanation: >-
      Specific withdrawal-related indication.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      First-line treatment of catatonia in the older adults consists of benzodiazepines, often
      at lower doses than among younger adults, and ECT.
    explanation: >-
      Population-specific dosing and treatment considerations.
- name: Electroconvulsive therapy
  description: >-
    ECT is a first-line option alongside benzodiazepines and is recommended when benzodiazepines
    have not produced remission. Choice and urgency depend on severity, underlying illness,
    tolerability and availability. Malignant catatonia may require urgent ECT when lorazepam
    is not rapidly effective. Four lorazepam nonresponders improved with ECT in an open prospective
    study, but this does not identify the biological mechanism of ECT. Severe respiratory disease
    may favor ECT as the initial treatment. Selected patients require maintenance ECT to prevent
    relapse.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: electroconvulsive therapy
    term:
      id: NCIT:C93303
      label: Electroconvulsive Therapy
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where benzodiazepines have not resulted in remission, ECT should be used.
    explanation: >-
      Guideline recommendation after inadequate benzodiazepine response.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      if benzodiazepines are not rapidly effective, ECT should be started within 48–72 h following
      the onset of malignant catatonia
    explanation: >-
      Addresses the urgency of escalation in malignant catatonia.
  - reference: PMID:8686484
    reference_title: Catatonia. II. Treatment with lorazepam and electroconvulsive therapy.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      Four patients failing lorazepam responded promptly to ECT.
    explanation: >-
      Small uncontrolled treatment observation, not evidence of a particular network or transmitter
      mechanism.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In severe respiratory disease, consider giving ECT as a first-line treatment rather than
      benzodiazepines.
    explanation: >-
      Conditional respiratory-disease recommendation.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      For certain patients, maintenance ECT following response to the acute course of ECT can
      help prevent relapse of catatonia.
    explanation: >-
      Supports a maintenance role in selected patients.
- name: Treatment of the underlying condition
  description: >-
    Treat an identified underlying psychiatric or medical disorder alongside catatonia-specific
    treatment and supportive care. Management depends on the cause and may include immunotherapy
    for autoimmune encephalitis or removal of a precipitating medication. Catatonia treatment
    need not await every investigation result.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Therapeutic Procedure
    term:
      id: NCIT:C49236
      label: Therapeutic Procedure
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Catatonia treatment should consist of specific treatment for the catatonia, treatment
      of any underlying disorder and prevention and management of complications of catatonia.
    explanation: >-
      The guideline explicitly describes all three components of management.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Treatment for catatonia should be instituted quickly after identification of catatonia
      and it is not always necessary to await results of all investigations before commencing
      treatment.
    explanation: >-
      Etiological evaluation and urgent symptomatic treatment can proceed together.
- name: Amantadine and memantine
  description: >-
    Amantadine or memantine may be considered when first-line benzodiazepine and ECT approaches
    are unavailable, cautioned, ineffective or only partly effective. Both antagonize NMDA receptors;
    amantadine also has dopaminergic effects. Proposed circuit explanations remain hypotheses.
    Reported benefits mainly come from case reports and small series, with possible publication
    bias. Their use does not establish NMDA hyperactivity as a general cause of catatonia or
    a mechanism-specific treatment for anti-NMDA receptor encephalitis. Amantadine requires
    particular caution in patients at seizure risk or with renal disease.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: amantadine
      term:
        id: CHEBI:2618
        label: amantadine
    - preferred_term: memantine
      term:
        id: CHEBI:64312
        label: memantine
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where first-line therapies for catatonia are unavailable, cautioned, ineffective or only
      partially effective, consider a trial of an NMDA receptor antagonist, either amantadine
      or memantine.
    explanation: >-
      Recommendation includes the availability and tolerability of first-line options, not just
      lorazepam failure.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      A bias towards the non-reporting of negative results must be considered, making the lack
      of RCTs and controlled studies an important shortcoming.
    explanation: >-
      The guideline qualifies its synthesis of amantadine and memantine reports.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Amantadine lowers the seizure threshold and should be used cautiously in patients at increased
      risk for seizures, including epilepsy and anti-NMDA receptor antibody encephalitis
    explanation: >-
      Clinical caution is particularly relevant to the autoimmune subgroup.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Amantadine is not dialyzable and thus should also be used cautiously in patients with
      renal disease.
    explanation: >-
      Supports the renal-disease caution.
  notes: >-
    The BAP guideline summarizes uncontrolled reports. Its proposed NMDA circuit mechanism is
    distinct from antibody-associated receptor dysfunction and is not treated as proof of a
    shared mechanism.
- name: Antipsychotic medication review
  description: >-
    Antipsychotics can induce or worsen catatonia and increase concern for neuroleptic malignant
    syndrome. Avoid them when there is no underlying psychotic disorder; discontinue dopamine
    antagonists in malignant catatonia. When treating coexisting psychosis, the guideline allows
    cautious second-generation antipsychotic use after an individual assessment, gradual titration
    and consideration of a benzodiazepine. For antipsychotic-induced catatonia, discontinuation
    is the primary intervention; if an antipsychotic remains necessary after treatment, restart
    cautiously.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Antipsychotic medications should be avoided where there is no underlying psychotic disorder.
    explanation: >-
      Avoidance is context-specific.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In malignant catatonia, discontinue all dopamine antagonists.
    explanation: >-
      Malignant catatonia requires a stronger avoidance recommendation.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      If antipsychotic medications are used, a SGA should be used with gradual titration, and
      co-administration of a benzodiazepine should be considered.
    explanation: >-
      The guideline permits carefully assessed treatment of underlying psychosis.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      When catatonia is attributed to antipsychotic administration, consider discontinuing the
      antipsychotic.
    explanation: >-
      Supports withdrawal of the precipitating medication.
- name: Supportive care and prevention of complications
  description: >-
    Provide hydration and nutritional support according to need, assess swallowing and consider
    assisted feeding, prevent pressure injury, and assess venous thromboembolism risk with prophylaxis
    when appropriate. Monitoring and supportive care accompany treatment of catatonia and its
    underlying cause.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Guidance has been developed for averting such complications, which include recommendations
      such as pharmacological thromboprophylaxis, frequent assessment of pressure areas, stretching
      to avoid muscle contractures and consideration of artificial feeding
    explanation: >-
      Guideline synthesis of measures that prevent complications of prolonged catatonia.
- name: Clozapine in selected contexts
  description: >-
    Restarting clozapine is recommended when its withdrawal precipitates catatonia, if clinically
    feasible, with re-titration after an interruption. ECT is another option. Clozapine may
    also be considered for chronic mild catatonia associated with schizophrenia. These indications
    do not justify routine antipsychotic treatment of catatonia without psychosis; the evidence
    is largely uncontrolled.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: clozapine
      term:
        id: CHEBI:3766
        label: clozapine
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where catatonia has resulted from clozapine withdrawal, restart clozapine if possible
      and, if necessary, use ECT.
    explanation: >-
      Specific withdrawal-related recommendation.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      If catatonia is chronic and mild in the context of schizophrenia, consider a trial of
      clozapine.
    explanation: >-
      A separate, restricted clinical context for clozapine.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      If clozapine therapy is interrupted for more than 48 hours, re-titration from a typical
      starting dose
    explanation: >-
      Re-initiation must account for the interruption rather than simply restoring a previous
      maintenance dose.
- name: Lithium maintenance for periodic catatonia
  description: >-
    Lithium may be considered to prevent recurrent episodes of periodic catatonia. This maintenance
    indication rests on case reports and small case series, rather than controlled proof of
    efficacy for catatonia generally.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: lithium(1+)
      term:
        id: CHEBI:49713
        label: lithium(1+)
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In the maintenance phase of periodic catatonia, consider prophylactic treatment with lithium.
    explanation: >-
      Conditional maintenance recommendation.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Lithium is the most frequently reported agent used in the maintenance of periodic catatonia,
      but even this evidence relies only on case reports and small case series
    explanation: >-
      States the evidence limitation.
- name: Zolpidem
  description: >-
    Zolpidem has been used as a diagnostic or therapeutic challenge and as an alternative treatment
    in case reports, including after inadequate lorazepam or ECT response. Reported effects
    are often transient; this is not an established substitute for first-line treatment.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: zolpidem
      term:
        id: CHEBI:10125
        label: zolpidem
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      When a diagnosis of catatonia is uncertain, a diagnostic challenge using zolpidem may
      be considered.
    explanation: >-
      Conditional diagnostic use.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Mastain et al. (1995) described a serendipitous dramatic response to oral zolpidem 10
      mg in a woman with a subcortical stroke whose catatonia was largely unresponsive to lorazepam
      or ECT.
    explanation: >-
      The guideline describes an uncontrolled treatment observation.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The response is transitory, as with benzodiazepines, and is usually observed for 3–6 h
    explanation: >-
      Limits interpretation of the reported response duration.
- name: Carbamazepine
  description: >-
    Carbamazepine is a lower-evidence option when first-line treatments and NMDA receptor antagonists
    are unavailable, cautioned or insufficient. Evidence consists of case reports and small
    series, often in patients with mood disorders; interactions and adverse effects require
    consideration.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: carbamazepine
      term:
        id: CHEBI:3387
        label: carbamazepine
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Three articles have reported using carbamazepine to treat catatonia in seven cases
    explanation: >-
      Small uncontrolled evidence base.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Carbamazepine is less commonly used due to concerns of side effects and drug-drug interactions.
    explanation: >-
      Explains a limitation of this alternative.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective
      or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine,
      valproate, topiramate or a SGA.
    explanation: >-
      Low-grade BAP recommendation for later-line options, not a head-to-head demonstration
      of efficacy.
- name: Valproic acid
  description: >-
    Valproate has been used as an adjunct or alternative in catatonia, including excited presentations.
    The evidence is limited to case reports and series. It may also address a comorbid mood
    disorder; reproductive risks matter when selecting treatment.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: valproic acid
      term:
        id: CHEBI:39867
        label: valproic acid
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Valproic acid use in catatonia has been reported in four papers in which five patients
      were suffering with psychoses, mostly schizophrenia spectrum in nature. In three instances,
      excited catatonia was noted as part of the presentation.
    explanation: >-
      Describes the small and selected reported clinical population.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Valproate may be a good option for catatonia patients with comorbid bipolar disorder;
      however, caution should be used in women of childbearing potential due to the risk for
      teratogenic effects and polycystic ovary syndrome.
    explanation: >-
      Contextual benefit and safety considerations from expert synthesis.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective
      or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine,
      valproate, topiramate or a SGA.
    explanation: >-
      Low-grade BAP recommendation for later-line options, not a head-to-head demonstration
      of efficacy.
- name: Topiramate
  description: >-
    Topiramate has been reported as an adjunct to benzodiazepines in a small case series. It
    is a lower-evidence option when established treatments and NMDA antagonists cannot be used
    or have been insufficient.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: topiramate
      term:
        id: CHEBI:63631
        label: topiramate
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Another case series involving four cases highlighted the benefits of topiramate in the
      treatment of catatonia
    explanation: >-
      Identifies the limited study design.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Topiramate was used as an adjunctive treatment along with a benzodiazepine.
    explanation: >-
      Supports adjunctive rather than established monotherapy use.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective
      or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine,
      valproate, topiramate or a SGA.
    explanation: >-
      Low-grade BAP recommendation for later-line options, not a head-to-head demonstration
      of efficacy.
- name: Repetitive transcranial magnetic stimulation
  description: >-
    rTMS is an investigational alternative when ECT is indicated but unavailable. Case reports
    and small series suggest benefit, but establish neither comparative efficacy nor the optimal
    stimulation target.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: Repetitive Transcranial Magnetic Stimulation
    term:
      id: NCIT:C154664
      label: Repetitive Transcranial Magnetic Stimulation
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where ECT is indicated but unavailable, consider treatment with rTMS or tDCS.
    explanation: >-
      Conditional recommendation supported mainly by case reports and case series; not established
      equivalence to ECT.
- name: Transcranial direct current stimulation
  description: >-
    tDCS is an investigational neuromodulation option when ECT is indicated but unavailable.
    Available case reports and series do not establish its comparative efficacy.
  therapeutic_modality: DEVICE
  treatment_term:
    preferred_term: Transcranial Direct Current Stimulation
    term:
      id: NCIT:C129862
      label: Transcranial Direct Current Stimulation
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where ECT is indicated but unavailable, consider treatment with rTMS or tDCS.
    explanation: >-
      Conditional recommendation supported mainly by case reports and case series; not established
      equivalence to ECT.
- name: 'Dopaminergic agents: conflicting guidance'
  description: >-
    Levodopa and dopamine agonists have been tried in isolated cases. The BAP guideline lists
    them as low-evidence later-line possibilities, whereas the 2025 APA resource document discourages
    them because of reported worsening of psychosis. They are not established routine treatments
    for catatonia, and their use does not prove a general dopamine-deficiency mechanism.
  therapeutic_modality: SMALL_MOLECULE
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Where first-line therapies and NMDA receptor antagonists are unavailable, cautioned, ineffective
      or only partially effective, consider a trial of levodopa, a dopamine agonist, carbamazepine,
      valproate, topiramate or a SGA.
    explanation: >-
      BAP conditional, low-grade recommendation.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Dopamine agonists, including stimulants and carbidopa-levodopa, have also been used with
      some success for catatonia, though nearly all patients have noted worsening of psychotic
      symptoms; as such, they are not recommended
    explanation: >-
      The APA authors draw a different clinical recommendation from the limited reports; the
      entry preserves this disagreement.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: levodopa
      term:
        id: CHEBI:15765
        label: L-dopa
- name: Psychological support for mild catatonia in autism
  description: >-
    In autistic people with mild catatonia, psychological interventions and/or lorazepam may
    be considered. Moderate or severe presentations require consideration of benzodiazepines
    and/or ECT. Assessment must first establish a marked change from the individual's baseline
    autistic traits.
  therapeutic_modality: BEHAVIORAL
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      First-line interventions in mild cases of catatonia are psychological interventions and/or
      lorazepam, but the standard treatments for catatonia (i.e. benzodiazepines in escalating
      dosages and/or bilateral ECT) should be considered in moderate to severe cases.
    explanation: >-
      This recommendation occurs in the guideline section on autism, not as a general substitute
      for treatment of severe catatonia.
  treatment_term:
    preferred_term: Psychotherapy
    term:
      id: NCIT:C15308
      label: Psychotherapy
- name: Oxazepam
  description: >-
    Oxazepam improved severe psychomotor retardation and mutism in a small double-blind crossover
    comparison with lorazepam. The study population was defined by these symptoms, so its findings
    should not be treated as proof of equivalence across all catatonia presentations. Lorazepam
    remains the usual first choice.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: oxazepam
      term:
        id: CHEBI:7823
        label: oxazepam
  evidence:
  - reference: PMID:10435212
    reference_title: A double-blind comparison of lorazepam and oxazepam in psychomotor retardation and mutism.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      Twenty-one hospitalized patients with severe psychomotor retardation and mutism were treated
      with 2 mg LO and 60 mg OX in a double-blind crossover study design.
    explanation: >-
      Defines the selected study population and comparator design.
  - reference: PMID:10435212
    reference_title: A double-blind comparison of lorazepam and oxazepam in psychomotor retardation and mutism.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      Both benzodiazepines significantly reduced psychomotor symptoms.
    explanation: >-
      Supports symptom improvement without a general noninferiority claim.
  - reference: PMID:10435212
    reference_title: A double-blind comparison of lorazepam and oxazepam in psychomotor retardation and mutism.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      The second time, however, LO was significantly better compared with OX in alleviating
      the target symptoms.
    explanation: >-
      Preserves the sequence-related difference rather than asserting equal effects.
- name: Ketamine and esketamine
  description: >-
    Ketamine and esketamine are experimental treatments supported by a small, heterogeneous
    published case literature, predominantly involving retarded catatonia and underlying mood
    disorders. A systematic review assembled 25 patients; reported improvements do not establish
    controlled efficacy or general safety. Dissociative adverse effects can limit treatment.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: ketamine
      term:
        id: CHEBI:6121
        label: ketamine
    - preferred_term: esketamine
      term:
        id: CHEBI:60799
        label: esketamine
  evidence:
  - reference: PMID:39098303
    reference_title: 'Ketamine for catatonia: A novel treatment for an old clinical challenge? A systematic review of the evidence.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      Twenty articles were included, encompassing a total of 25 catatonic patients receiving
      ketamine or esketamine.
    explanation: >-
      Small systematic aggregation of the published clinical literature.
  - reference: PMID:39098303
    reference_title: 'Ketamine for catatonia: A novel treatment for an old clinical challenge? A systematic review of the evidence.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      patients mostly exhibited manifestations compatible with the retarded subtype of catatonia.
      Mood disorders were the most prevalent underlying diagnoses.
    explanation: >-
      Limits applicability to the reported clinical mix.
  - reference: PMID:39098303
    reference_title: 'Ketamine for catatonia: A novel treatment for an old clinical challenge? A systematic review of the evidence.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      Only one patient discontinued treatment due to intolerable dissociative effects.
    explanation: >-
      Reports an observed tolerability limitation; the small dataset cannot exclude other risks.
- name: Sodium oxybate under investigation
  description: >-
    Sodium oxybate is being evaluated against continued lorazepam in the Laborit randomized
    trial for lorazepam-resistant catatonia associated with psychiatric disorders. The published
    protocol proposes GABA-B-mediated benefit but reports no randomized efficacy results. Its
    restricted eligibility and respiratory monitoring requirements limit generalization, particularly
    to malignant or medically caused catatonia.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: sodium oxybate
      term:
        id: CHEBI:749298
        label: sodium oxybate
  evidence:
  - reference: PMID:40705436
    reference_title: 'Sodium Oxybate as a Potential New Treatment for Catatonia in Patients With Depression, Bipolar Disorder, or a Psychotic Disorder: Protocol for a Randomized Controlled Trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      This study aims to provide robust evidence on the efficacy and safety of sodium oxybate
      for treating catatonia unresponsive to lorazepam
    explanation: >-
      A research objective, not an established treatment effect.
  - reference: PMID:40705436
    reference_title: 'Sodium Oxybate as a Potential New Treatment for Catatonia in Patients With Depression, Bipolar Disorder, or a Psychotic Disorder: Protocol for a Randomized Controlled Trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      We hypothesize that pharmacological therapies, aimed at increasing GABA-B–mediated neurotransmission,
      could be effective in patients with lorazepam-resistant catatonia.
    explanation: >-
      Mechanistic rationale remains a hypothesis.
  - reference: PMID:40705436
    reference_title: 'Sodium Oxybate as a Potential New Treatment for Catatonia in Patients With Depression, Bipolar Disorder, or a Psychotic Disorder: Protocol for a Randomized Controlled Trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      This study focuses on semiacute catatonic episodes caused by either psychotic or affective
      disorders; hence, chronic catatonia and patients with underlying somatic disorders are
      excluded.
    explanation: >-
      Defines the protocol population.
  - reference: PMID:40705436
    reference_title: 'Sodium Oxybate as a Potential New Treatment for Catatonia in Patients With Depression, Bipolar Disorder, or a Psychotic Disorder: Protocol for a Randomized Controlled Trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      Patients will be closely monitored for side effects, with particular attention to respiratory
      problems
    explanation: >-
      Planned safety monitoring is not evidence of established safety.
- name: Patient and caregiver education
  description: >-
    Explain that catatonia is treatable and can impair communication and voluntary initiation.
    Teach families to recognize new motor or behavioral changes and recurrence, and coordinate
    psychiatric, neurological, nursing and rehabilitation care.
  therapeutic_modality: BEHAVIORAL
  evidence:
  - reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK430842/
    reference_title: Catatonia - StatPearls - NCBI Bookshelf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      After remission, families should be counseled on monitoring for recurrence, particularly
      in individuals with mood disorders or those with a prior catatonic episode.
    explanation: >-
      Practical follow-up advice from the clinical overview.
differential_diagnoses:
- name: Neuroleptic malignant syndrome
  description: >-
    Neuroleptic malignant syndrome overlaps with malignant catatonia in rigidity, hyperthermia,
    altered mental state and autonomic dysfunction. Some experts consider dopamine-blocker-associated
    NMS a form of malignant catatonia.
  distinguishing_features:
  - A temporal relationship to a dopamine receptor blocking medication supports NMS; malignant catatonia can occur without this exposure.
  - Suspected NMS requires immediate cessation of dopamine blocking medications and urgent treatment.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      many experts consider neuroleptic malignant syndrome (NMS) to be a type of malignant catatonia
      that is precipitated by dopamine receptor blocking agents.
    explanation: >-
      The resource document describes the exposure relationship and diagnostic overlap.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      When NMS is suspected, immediate cessation of antipsychotic and other dopamine blocking
      medications is imperative.
    explanation: >-
      Identifies an immediate management implication of this differential.
- name: Delirium
  description: >-
    Hypoactive delirium can resemble hypokinetic catatonia, and hyperactive delirium can resemble
    excited catatonia. The conditions can coexist; diagnostic manuals differ in how this is
    represented.
  distinguishing_features:
  - Fluctuating arousal, impaired attention and cognitive disturbance favor delirium; additional catalepsy, posturing or echophenomena support assessment for coexisting catatonia.
  - An EEG may support delirium assessment, but does not replace clinical evaluation.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Distinguishing features of delirium include impaired or fluctuating level of arousal,
      attention, and other cognitive disturbances. EEG can be helpful to confirm the diagnosis
      of delirium.
    explanation: >-
      Supports the cognitive distinction in hyperactive presentations.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Classic findings more specific to catatonia are often helpful in identifying catatonia
      in patients with or at risk for delirium.
    explanation: >-
      Supports assessment for both conditions rather than treating them as mutually exclusive.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the ICD-11 recognizes catatonia as a distinct condition and allows for the co-diagnosis
      of both delirium and catatonia if they occur simultaneously.
    explanation: >-
      Clarifies that the nosological distinction is not a biological exclusion.
- name: Akinetic mutism and abulia
  description: >-
    Reduced volition after neurological injury can markedly reduce spontaneous movement and
    speech, resembling hypokinetic catatonia.
  distinguishing_features:
  - Neurological injury and severe reduction in spontaneous movement and speech support an abulic or akinetic-mutism syndrome.
  - Additional positive catatonic signs, particularly catalepsy, posturing or echophenomena, favor a catatonic component; a lorazepam response alone is not a specific discriminator.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      This disorder, characterized by reduced or absent volition, is typically due to neurologic
      injury affecting the ventromedial prefrontal cortex or anterior cingulate cortex (e.g.,
      stroke, traumatic brain injury). Patients exhibit severe reductions in spontaneous movement
      and speech, which can resemble catatonia.
    explanation: >-
      Describes the neurological context and clinical overlap without treating reduced speech
      as an exclusion.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      the positive features of catatonia (such as echophenomena, catalepsy and posturing) may
      have greater discriminatory value than some of the negative features (such as mutism and
      stupor). Challenge tests are useful in many situations
    explanation: >-
      General differential principle from the BAP guideline, not a test validated specifically
      against abulia.
- name: Late-stage Parkinson disease
  description: >-
    Advanced Parkinson disease may cause immobility, rigidity and markedly reduced speech that
    resemble hypokinetic catatonia.
  distinguishing_features:
  - Established Parkinson disease, resting tremor, postural instability, levodopa responsiveness and supportive dopamine transporter imaging help distinguish the underlying movement disorder.
  - These findings do not establish a shared degenerative mechanism for catatonia.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      These patients have a known diagnosis of PD and other distinguishing features of PD, including
      resting tremor, positive response to levodopa and postural instability, and/or a positive
      dopamine transporter scan
    explanation: >-
      The document identifies disease history and parkinsonian features as discriminators, not
      a universal catatonia mechanism.
- name: Locked-in syndrome
  description: >-
    Patients can be immobile and mute while retaining the motivation to communicate.
  distinguishing_features:
  - Attempts to communicate through preserved eye movements support locked-in syndrome.
  - Brain MRI can identify the responsible brainstem lesion.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      These patients are often motivated to try to communicate with eye movements (which may
      be their only residual voluntary movements)
    explanation: >-
      Identifies a useful bedside feature without claiming every patient retains identical movements.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Locked-in syndrome is caused by brainstem lesions identified on brain MRI.
    explanation: >-
      Supports structural imaging in the differential.
- name: Serotonin syndrome
  description: >-
    Serotonin syndrome can resemble malignant catatonia through autonomic instability, hyperthermia
    and rigidity.
  distinguishing_features:
  - A history of serotonergic agents and their doses is central to assessment.
  - Hyperreflexia, myoclonus and gastrointestinal symptoms support serotonin syndrome.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Hyperreflexia, myoclonus, and gastrointestinal symptoms can help to identify SS. Quantification
      of use and doses of all serotoninergic agents taken prior to presentation is necessary.
    explanation: >-
      Provides specific distinguishing features and the relevant exposure history.
- name: Stiff-person syndrome
  description: >-
    Muscle stiffness and spasms can limit movement and resemble catatonic rigidity. Both syndromes
    may improve with benzodiazepines.
  distinguishing_features:
  - Emotional stress can exacerbate stiffness and spasms in stiff-person syndrome.
  - Preserved speech and cognition are typical, and elevated glutamic acid decarboxylase antibodies support the diagnosis.
  - Benzodiazepine responsiveness does not separate these conditions.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      The condition is exacerbated by emotional stress. Symptoms such as limited movement and
      positive response to benzodiazepines in SPS can somewhat resemble hypoactive catatonia.
      SPS differs from catatonia in that these patients are verbal and are typically fully cognitively
      intact. A diagnosis of SPS is supported by elevated levels of glutamic acid decarboxylase
      (GAD) antibodies
    explanation: >-
      Supports clinical and antibody distinctions while qualifying the nonspecific treatment
      response.
- name: Akathisia
  description: >-
    Motor restlessness can resemble excited catatonia, including after dopamine blocking medication
    exposure.
  distinguishing_features:
  - Patients often describe inner restlessness and discomfort driving the movements.
  - Other catatonic signs are usually absent.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      patients with akathisia will often describe an inner state of restlessness and discomfort
      that leads to and perpetuates the motor symptoms.
    explanation: >-
      Supports the subjective restlessness distinction.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      patients with akathisia will not typically exhibit any other signs of catatonia.
    explanation: >-
      Qualifies the distinction as typical rather than absolute.
- name: Major neurocognitive disorders
  description: >-
    Advanced neurocognitive disorders may cause hypokinesis and mutism. Catatonia can also occur
    as a superimposed syndrome.
  distinguishing_features:
  - Longitudinal cognitive decline across multiple domains supports an underlying neurocognitive disorder.
  - Posturing, catalepsy and waxy flexibility suggest coexisting catatonia rather than dementia alone.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      In later stages of major neurocognitive disorder (MNCD)/dementia, patients can develop
      hypokinesis and mutism. However, they do not develop classic specific catatonia symptoms
      such as posturing, catalepsy and waxy flexibility unless comorbid catatonia is present.
    explanation: >-
      Supports assessment for a superimposed catatonic syndrome.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Obtaining a chronological history of clinical progression can be clarifying, given that
      most MNCDs tend to develop and worsen over time.
    explanation: >-
      Supports the longitudinal distinction without claiming all catatonia is acute or episodic.
- name: Mania
  description: >-
    Mania and hyperkinetic catatonia can both produce agitation, excitation and excessive or
    disorganized speech. Severe mania may coexist with catatonia.
  distinguishing_features:
  - Manic agitation may be goal-directed, whereas catatonic agitation is not.
  - The presence of mania does not exclude additional catatonic signs.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      One distinguishing feature is that agitation in catatonia is not goal-directed, whereas
      a manic episode may include goal-directed agitation. It is important to keep in mind that
      a severe manic episode and catatonia may co-occur.
    explanation: >-
      Retains the conditional nature of the clinical distinction.
- name: Anti-NMDA receptor encephalitis
  description: >-
    Anti-NMDA receptor encephalitis can cause a full catatonic syndrome or some overlapping
    signs, including autonomic instability. It is an etiological consideration as well as a
    diagnostic overlap.
  distinguishing_features:
  - A partial or absent lorazepam response does not exclude catatonia associated with anti-NMDA receptor encephalitis.
  - When the cause of catatonia is unclear, the etiological workup may include serum and CSF neuronal autoantibodies.
  evidence:
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      This condition may present with full spectrum catatonia, or patients may have only some
      of the classic symptoms of catatonia, including autonomic instability
    explanation: >-
      Identifies encephalitis as a potential cause of catatonia, not solely a mimic.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      incomplete response to a lorazepam challenge test, and some patients
      with catatonia may not experience a clinical response to lorazepam at all.
    explanation: >-
      Limits the interpretation of a negative challenge test.
- name: Nonconvulsive status epilepticus
  description: >-
    Nonconvulsive status epilepticus may present as catatonia and can be clinically difficult
    to distinguish.
  distinguishing_features:
  - Subtle facial or limb twitching, neurological disease and medication changes affecting seizure threshold increase suspicion.
  - EEG is important when this differential is suspected.
  - Improvement with a lorazepam challenge is not specific because both conditions may respond.
  evidence:
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      there is a clear case for an electroencephalogram (EEG) in the context of possible non-convulsive
      status epilepticus (NCSE), which can present as catatonia
    explanation: >-
      Supports EEG assessment for this potentially treatable mimic.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Red flags for NCSE include subtle ictal phenomena (such as twitching of the face or extremities),
      comorbid neurological disease and a change in medications that affect seizure threshold
    explanation: >-
      Supplies specific clues to seizure activity.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      stiff person syndrome and NCSE are likely to improve with a lorazepam challenge.
    explanation: >-
      A positive challenge alone cannot distinguish these syndromes.
discussions:
- discussion_id: catatonia_no_unified_mechanism
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Distributed Psychomotor Network Destabilization
  prompt: >-
    Is there a single mechanism or biomarker that accounts for catatonia across
    its psychiatric, neurologic, autoimmune, and medical contexts, or is the
    convergent-network account the correct final level of explanation?
  rationale: >-
    Catatonia occurs across heterogeneous etiologies, and the available imaging and pharmacological
    observations do not establish a single causal mechanism. The distributed-network model is
    an integrative hypothesis. Studies across causes and acute clinical states are needed to
    test shared network changes and determine whether useful biomarkers are syndrome-wide or
    restricted to particular etiologies.
  proposed_experiments:
  - experiment_id: exp_catatonia_acute_state_multimodal_cohort
    name: Prospective acute-state multimodal phenotyping across upstream causes
    description: >-
      Recruit an acute-state catatonia cohort stratified by upstream cause
      (mood disorder, schizophrenia-spectrum, autoimmune encephalitis, medical
      or drug-induced) and acquire the same multimodal battery in every stratum:
      resting-state and emotional-task fMRI, GABA-A receptor imaging, striatal
      dopaminergic imaging, CSF and serum neuronal autoantibodies, and
      dimensional Bush-Francis and Northoff scale scoring. The discriminating
      test is whether the network signature is shared across strata while the
      neurochemical signature differs by stratum — the prediction of the
      convergent model — or whether each stratum has its own network signature.
  evidence:
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      No single biomarker or unified mechanism fully accounts for catatonia
      across contexts.
    explanation: >-
      The explicit statement of the gap this discussion records.
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Future progress will depend on dimensional phenotyping, multimodal
      biomarker integration, and subtype-sensitive treatment research.
    explanation: >-
      The authors' own statement of what would close the gap, which the
      proposed experiment operationalizes.
- discussion_id: catatonia_sampling_and_acute_state_bias
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Distributed Psychomotor Network Destabilization
  - pathophysiology#Orbitofrontal Emotional-Motor Processing Dysfunction
  prompt: >-
    How much of the imaging evidence for the distributed-network model is an
    artifact of studying schizophrenia-spectrum patients in the post-acute
    state rather than catatonia in the acute state across its full diagnostic
    range?
  rationale: >-
    Schizophrenia-spectrum and postacute samples dominate the cited imaging studies. Persistent
    orbitofrontal changes could reflect predisposition, illness consequences or treatment; the
    study design does not establish which. Generalization to acute catatonia across etiologies
    requires prospective comparison.
  evidence:
  - reference: PMID:42431537
    reference_title: "Toward a systems model of catatonia: Circuits, neurochemistry, immune perturbation, and biological heterogeneity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      key limitations remain, including the overrepresentation of
      schizophrenia-spectrum samples and limited acute-state data
    explanation: >-
      Names both sampling limitations directly.
  - reference: PMID:15279056
    reference_title: "Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Because we investigated postacute patients, orbitofrontal cortical
      alterations may be interpreted as a trait marker predisposing for
      development of catatonic syndrome
    explanation: >-
      A worked instance of the acute-state limitation, stated by the original
      authors.
- discussion_id: catatonia_evidence_quality_ceiling
  kind: KNOWLEDGE_GAP
  status: OPEN
  attaches_to:
  - pathophysiology#Distributed Psychomotor Network Destabilization
  prompt: >-
    Can adequately controlled and reported trials improve the predominantly observational treatment
    evidence for catatonia?
  rationale: >-
    The BAP guideline identifies several randomized trials but describes small samples, high
    risk of bias, incomplete reporting and restricted populations. The quoted lorazepam response
    proportion comes from an open prospective study, not a controlled treatment effect. A small
    number of trials should not be described as an absence of randomized research.
  evidence:
  - reference: PMID:37039129
    reference_title: "Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Clinical trials were uncommon, and the recommendations in this guideline
      are mainly informed by small observational studies, case series and case
      reports, which highlights the need for randomised controlled trials and
      prospective cohort studies in this area.
    explanation: >-
      The guideline's own statement of the evidence ceiling.
  - reference: PMID:37039129
    reference_title: 'Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Several RCTs have been conducted, but they have usually been at high risk of bias, inadequately
      reported, using outdated treatments or applicable to only a small subset of patients with
      catatonia
    explanation: >-
      Distinguishes a limited trial literature from no randomized evidence.
- discussion_id: catatonia_malignant_vs_nms
  kind: CONTROVERSY
  status: OPEN
  attaches_to:
  - pathophysiology#Autonomic Decompensation
  - pathophysiology#Reduced Striatal Dopaminergic Transmission
  prompt: >-
    Does neuroleptic malignant syndrome represent a medication-triggered form of malignant catatonia,
    or do the overlapping clinical syndromes have distinguishable mechanisms?
  rationale: >-
    The syndromes overlap in rigidity, hyperthermia, altered mental state and autonomic dysfunction.
    Dopamine-blocker exposure supports NMS, whereas malignant catatonia can arise without it.
    Some experts consider NMS a form of malignant catatonia; the shared-dopamine model remains
    a hypothesis rather than an established mechanistic discriminator.
  evidence:
  - reference: PMID:40966690
    reference_title: Reduced striatal dopamine transmission as a transdiagnostic substrate of psychomotor retardation.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In addition, there are close epidemiological relationships between
      depression and Parkinson's disease, and between catatonia and neuroleptic
      malignant syndrome.
    explanation: >-
      Records the epidemiological relationship that a shared-substrate account
      would explain.
  - reference: PMID:35861966
    reference_title: "Malignant Catatonia: A Review for the Intensivist."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Malignant catatonia describes catatonia that presents with clinically
      significant autonomic abnormalities including change in temperature, blood
      pressure, heart rate, and respiratory rate.
    explanation: >-
      Supplies the definition of the entity on the catatonia side of the
      controversy.
  - reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    reference_title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      many experts consider neuroleptic malignant syndrome (NMS) to be a type of malignant catatonia
      that is precipitated by dopamine receptor blocking agents.
    explanation: >-
      The resource document describes the exposure relationship and diagnostic overlap.
- discussion_id: catatonia_hpo_term_gap
  kind: CURATION_TODO
  status: OPEN
  attaches_to:
  - pathophysiology#Hypokinetic Psychomotor Output
  prompt: >-
    How should unbound catatonic signs be represented until specific HPO concepts are available?
  rationale: >-
    OLS4 HP searches on 2026-10-04 for catatonia, catalepsy and waxy flexibility returned no
    hits. Stupor returned coma and akinetic mutism, which are not equivalent; mannerism returned
    motor stereotypy and broader behavior terms. Echopraxia (HP:0020124) and Pressure ulcer
    (HP:0012399) have specific matching terms and are included. Query pattern: https://www.ebi.ac.uk/ols4/api/search?ontology=hp&q=catatonia;
    substitute each listed phrase, URL-encoding spaces. Unbound descriptors retain clinically
    important signs without false equivalences.
  notes: >-
    Upstream ontology gap, not a dismech bug. Recorded here so the decision is
    auditable rather than rediscovered.
notes: >-
  Catatonia is retained as a standalone transdiagnostic syndrome under MONDO:0800105. The organizing
  network model and transmitter-specific models remain incompletely established, and their causal
  links are explicitly provisional. Clinical signs, etiological associations and complications
  are distinguished from molecular mechanisms. Epidemiological estimates are scoped to their
  settings and case definitions. Treatment recommendations draw heavily on observational evidence
  and expert consensus, although a limited randomized-trial literature exists. The StatPearls
  overview contains inconsistent NMDA activation/hypofunction statements and describes specific
  periodic-catatonia mutations; the cited primary and specialist sources do not substantiate
  those assertions. Drug trials and selected mechanistic neuromodulation studies are distinguished
  from demonstrated treatment efficacy. Hypokinetic, hyperkinetic and parakinetic presentations
  are overlapping motor dimensions. Malignant catatonia is identified by autonomic decompensation
  and can accompany any motor presentation; periodic catatonia describes a recurrent course,
  with historical familial linkage evidence restricted to selected pedigrees. PMID:28613592
  and the NCBI NBK430842 URL identify the same StatPearls chapter; PMID:29140521 and the PMC6101628
  URL identify the same Solmi meta-analysis. The alternate URLs provide full text and are not
  independent publications.
references:
- reference: url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
  title: https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
- reference: PMID:28613592
  title: Catatonia.
  tags:
  - StatPearls
- reference: url:https://www.ncbi.nlm.nih.gov/sites/books/NBK430842/
  title: Catatonia - StatPearls - NCBI Bookshelf
  tags:
  - StatPearls
- reference: url:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101628/
  title: 'Prevalence of Catatonia and Its Moderators in Clinical Samples: Results from a Meta-analysis and Meta-regression Analysis - PMC'
clinical_trials:
- name: NCT02734498
  description: >-
    Study comparing right unilateral and bilateral ECT for catatonia, with a non-ECT comparison
    group. Recruitment was terminated; this record does not establish the superiority of one
    electrode placement.
  phase: NOT_APPLICABLE
  status: TERMINATED
  evidence:
  - reference: clinicaltrials:NCT02734498
    reference_title: Prospective Treatment Study of Catatonia Patients With Right Unilateral Electroconvulsive Treatment (RUL ECT) and Bilateral Electroconvulsive Treatment (BL ECT) Regimens
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      The purpose of this treatment study is to compare the effectiveness of different electrode
      placements used in Electroconvulsive Therapy (ECT) in the treatment of catatonia.
    explanation: >-
      The registry summary documents the study objective, not a demonstrated clinical effect.
  notes: >-
    Registry phase and status checked through ClinicalTrials.gov API v2 on 2026-10-04. The registry
    reports termination because enrollment was unsuccessful; limited posted results should not
    be interpreted as an adequately powered comparison.
- name: NCT03116425
  description: >-
    Proof-of-concept study of personalized rTMS targets informed by functional MRI for chronic
    treatment-resistant catatonia.
  phase: NOT_APPLICABLE
  status: UNKNOWN
  evidence:
  - reference: clinicaltrials:NCT03116425
    reference_title: Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia - A Proof of Concept Study
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      Investigators hypothesize that personalizing rTMS targets using functional MRI will allow
      to improve symptoms of patients suffering from chronic catatonia.
    explanation: >-
      The registry summary documents the study objective, not a demonstrated clinical effect.
  notes: >-
    Registry phase and status checked through ClinicalTrials.gov API v2 on 2026-10-04. Current
    registry status is UNKNOWN; historical recruitment labels are not treated as current.
- name: NCT06139432
  description: >-
    CATATOES study evaluating active versus sham tDCS for catatonia.
  phase: NOT_APPLICABLE
  status: UNKNOWN
  evidence:
  - reference: clinicaltrials:NCT06139432
    reference_title: 'Catatonia: Effectiveness of Transcranial Direct Current Electrostimulation (CATATOES)'
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      Our objective is to evaluate the efficacy of tDCS in catatonia in a clinical trial.
    explanation: >-
      The registry summary documents the study objective, not a demonstrated clinical effect.
  notes: >-
    Registry phase and status checked through ClinicalTrials.gov API v2 on 2026-10-04. Current
    registry status is UNKNOWN.
- name: NCT06176456
  description: >-
    Placebo-controlled study evaluating the effectiveness and safety of TMS in catatonia.
  phase: NOT_APPLICABLE
  status: UNKNOWN
  evidence:
  - reference: clinicaltrials:NCT06176456
    reference_title: Interventional Triple-negative Placebo-controlled Personalized Prospective Study "Evaluation of the Efficacy and Safety of Noninvasive Neuromodulation of TMS in Subjects With Catatonia"
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      Evaluation effectiveness and safety of TMS in subjects with catatonia
    explanation: >-
      The registry summary documents the study objective, not a demonstrated clinical effect.
  notes: >-
    Registry phase and status checked through ClinicalTrials.gov API v2 on 2026-10-04. Current
    registry status is UNKNOWN.
- name: NCT06016764
  description: >-
    MRI-targeted continuous theta-burst stimulation study investigating motor-cortex excitability
    and catatonic symptoms in autism. It is principally a mechanistic probe and does not establish
    treatment efficacy.
  phase: PHASE_I
  status: COMPLETED
  evidence:
  - reference: clinicaltrials:NCT06016764
    reference_title: Use of Magnetic Resonance Imaging and Continuous Theta Burst Stimulation for Catatonia in Autism
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      This application will use a participant's own individual brain magnetic resonance image
      to target the primary motor strip with transcranial magnetic stimulation; to determine
      if hyper-excitability of the brain directly correlates with symptoms of catatonia and
      social-emotional impairment in autism.
    explanation: >-
      The registry summary documents the study objective, not a demonstrated clinical effect.
  notes: >-
    Registry phase and status checked through ClinicalTrials.gov API v2 on 2026-10-04. Registry
    phase I and completed status are retained as registered. The primary excitability measure
    concerns motor-evoked potentials.
- name: NCT05662228
  description: >-
    Phase II trial comparing lorazepam, IVIG and tofacitinib in Down syndrome regression disorder,
    in which catatonia may occur. Its broader regression-disorder population does not establish
    efficacy of immunotherapy for catatonia generally.
  phase: PHASE_II
  status: COMPLETED
  evidence:
  - reference: clinicaltrials:NCT05662228
    reference_title: Mechanistic Investigation of Therapies for Down Syndrome Regression Disorder
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      The study evaluates the safety and efficacy of three currently prescribed therapies: lorazepam,
      intravenous immunoglobulin (IVIG) and tofacitinib.
    explanation: >-
      The registry summary documents the study objective, not a demonstrated clinical effect.
  notes: >-
    Registry phase and status checked through ClinicalTrials.gov API v2 on 2026-10-04. Completed
    registry record; no results were posted in the queried API record. The trial does not enroll
    a general transdiagnostic catatonia population.
- name: ISRCTN11236443
  description: >-
    The Laborit study combines an observational cohort with a single-blind randomized comparison
    of sodium oxybate and continued lorazepam after inadequate initial lorazepam response. The
    target randomized population has psychiatric-associated catatonia; malignant catatonia and
    underlying somatic causes are excluded. The protocol is not an efficacy report.
  phase: PHASE_III
  status: RECRUITING
  evidence:
  - reference: PMID:40705436
    reference_title: 'Sodium Oxybate as a Potential New Treatment for Catatonia in Patients With Depression, Bipolar Disorder, or a Psychotic Disorder: Protocol for a Randomized Controlled Trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      The Laborit trial consists of a cohort study and an embedded single-blind randomized controlled
      trial (RCT).
    explanation: >-
      Specifies the study design.
  - reference: PMID:40705436
    reference_title: 'Sodium Oxybate as a Potential New Treatment for Catatonia in Patients With Depression, Bipolar Disorder, or a Psychotic Disorder: Protocol for a Randomized Controlled Trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      A total of 42 patients will be randomly assigned to either the sodium oxybate group, after
      a 2-day lorazepam reduction period, or the continuation of lorazepam.
    explanation: >-
      Planned enrollment and comparator, not actual trial completion.
  - reference: PMID:40705436
    reference_title: 'Sodium Oxybate as a Potential New Treatment for Catatonia in Patients With Depression, Bipolar Disorder, or a Psychotic Disorder: Protocol for a Randomized Controlled Trial.'
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    directness: DIRECT
    quote_role: PRIMARY_RESULT
    snippet: >-
      As of March 2025, the first 4 participants have been included in the cohort, with no trial
      participants enrolled yet.
    explanation: >-
      Dated enrollment statement from the protocol publication; not current recruitment status.
  - reference: ICTRP:ISRCTN11236443
    reference_title: "Sodium oxybate as a potential new treatment for catatonia in patients with depression, bipolar disorder or a psychotic disorder"
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      The Laborit study combines a multicenter, cohort study on psychiatric patients with catatonia,
      enabling us to study the broad pallet of catatonia symptoms, course of catatonia, and
      their possible determinants, with an embedded randomized controlled trial, using sodium
      oxybate as a treatment for patients with catatonia.
    explanation: >-
      The WHO-normalized registry describes the planned cohort and embedded trial, not an efficacy
      result.
  - reference: ICTRP:ISRCTN11236443
    reference_title: "Sodium oxybate as a potential new treatment for catatonia in patients with depression, bipolar disorder or a psychotic disorder"
    supports: SUPPORT
    evidence_source: OTHER
    directness: DIRECT
    quote_role: BACKGROUND
    snippet: >-
      Recruitment status | Recruiting
    explanation: >-
      The ICTRP record last refreshed on 24 August 2026 reports recruiting status.
  notes: >-
    Phase III and recruiting status were confirmed in the WHO ICTRP record on 2026-10-04, last
    refreshed on 24 August 2026, and agree with the primary ISRCTN PDF last edited on 12 August
    2026. EudraCT 2021-004049-19 lists the predecessor record as transitioned. Recruitment status
    and the dated March 2025 protocol enrollment statement are separate observations. The ICTRP
    results-availability flag alone does not establish efficacy; neither the cached registry
    text nor the published protocol reports trial efficacy results.
📚

References & Deep Research

References

4
url:https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
https://www.psychiatry.org/getattachment/bd1b5149-2c2e-472c-8fa9-1e5e79aeb4d5/Resource-Document-on-Catatonia.pdf
No top-level findings curated for this source.
PMID:28613592
Catatonia.
No top-level findings curated for this source.
url:https://www.ncbi.nlm.nih.gov/sites/books/NBK430842/
Catatonia - StatPearls - NCBI Bookshelf
No top-level findings curated for this source.
url:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101628/
Prevalence of Catatonia and Its Moderators in Clinical Samples: Results from a Meta-analysis and Meta-regression Analysis - PMC
No top-level findings curated for this source.