Catatonia
Pages 154–158 · Figure 1.4 · Table 1.34
Definition and prevalence
- A neuropsychiatric disorder with a wide range of signs and symptoms covering focal and generalised motor activity, speech, affect, complex behaviour and autonomic function.
- Meta-analysis of international data from 74 studies (1935–2017, 107,304 individuals): overall pooled mean prevalence just over 9% in patients diagnosed with a range of psychiatric and medical conditions.
Three subtypes
| Retarded / stuporous | Decreased psychomotor behaviour |
|---|---|
| Excited | Agitation, combativeness, impulsivity and apparently purposeless overactivity |
| Malignant catatonia | A life-threatening state presenting as catatonia with clinically significant autonomic abnormalities: raised blood pressure and body temperature, and change in heart rate and respiratory rate |
Stupor (retarded form)
- Key features: mutism, rigidity, marked psychomotor retardation, negativism, posturing, waxy flexibility and catalepsy.
- Historically associated with schizophrenia, but stupor is also seen in depression and, less commonly, mania, alcohol or benzodiazepine withdrawal, and conversion disorder.
Treat promptly. If psychiatric stupor is left untreated, physical health complications are unavoidable and develop rapidly. Prompt treatment is crucial to prevent dehydration, venous thrombosis, pulmonary embolism, pneumonia and, ultimately, death.
Associated conditions
Most commonly: bipolar disorder, schizophrenia and major depressive disorder. May also be seen in postpartum psychosis, post-traumatic stress disorder, developmental disorders such as autism spectrum disorder, neurodegenerative conditions, and a range of medical conditions:
- subarachnoid haemorrhages
- basal ganglia disorders
- non-convulsive status epilepticus
- locked-in and akinetic mutism states
- endocrine and metabolic disorders (e.g. Wilson's)
- Prader–Willi syndrome
- antiphospholipid syndrome
- autoimmune encephalitis, such as anti-NMDAR encephalitis
- systemic lupus erythematosus
- infections (especially CNS infections)
- dementia
- drug withdrawal and toxic drug states (e.g. after abrupt withdrawal of clozapine, and withdrawal of zolpidem, benzodiazepines and many non-psychotropic medications, including medicines used in oncology)
Treatment — benzodiazepines
- Treatment of stupor in catatonia depends somewhat on its cause but should usually include benzodiazepines.
- Benzodiazepine monotherapy is the treatment of choice for stupor in the context of affective and conversion disorders.
- Postulated mechanism: increasing GABAergic transmission or reducing levels of brain-derived neurotrophic factor.
- Most clinical experience is with lorazepam. Many patients respond to standard doses (up to 4 mg/day), but repeated and higher doses (8–24 mg/day) may be needed.
- Small observational study (catatonic stupor in MDD or bipolar I disorder) using a lorazepam–diazepam protocol: response in 10 of 12 patients with IM lorazepam 2–4 mg.
- Another study with a very similar protocol: relief in 18 of 21 patients with catatonia caused by general medical conditions or substance misuse.
- Where benzodiazepines are effective, onset is rapid.
- A test dose of zolpidem (10 mg) may predict response to benzodiazepines, and frequent dosing of zolpidem may provide effective treatment. IV lorazepam has also been used to predict response.
Catatonia in schizophrenia
- Somewhat less likely to respond to benzodiazepines alone — response in 40–50% of cases.
- A double-blind, placebo-controlled crossover trial with lorazepam up to 6 mg/day showed no effect on chronic catatonic symptoms in established schizophrenia, similar to the poor effect of lorazepam in a non-randomised trial.
- A Cochrane review found only one eligible RCT (17 participants, lorazepam vs oxazepam): no clear difference in effect. No data were available comparing benzodiazepines with placebo or standard care.
Differential diagnosis: EPSEs and NMS
- In schizophrenia, the differential includes EPSEs and NMS. Debate continues over the similarities and differences between catatonic stupor in psychosis and NMS.
- Malignant catatonia may not be distinguishable from NMS, clinically or by laboratory testing — prompting the view that NMS may be a variant of malignant catatonia.
- However, NMS can probably be ruled out in the absence of any prior or recent administration of a dopamine antagonist.
Treatment — ECT and brain stimulation
- The vast majority of evidence suggests prompt ECT remains the most successful treatment for catatonia.
- ECT-responsive catatonia has been recognised in NMS, delirious mania, autism spectrum disorder and limbic encephalitis.
- Response to ECT may be lower in schizophrenia (or in those treated with antipsychotics) than in mood disorders, but ECT is still the treatment of choice for catatonic schizophrenia that has failed an adequate trial of benzodiazepines.
- Malignant catatonia: maximise the effect of ECT using liberal stimulus dosing to induce well-generalised seizures.
- Physical health needs should be prioritised, with inpatient medical care when necessary — especially for autonomic instability and for those whose dietary intake cannot be managed in psychiatric care.
- A 2024 systematic review of non-invasive brain stimulation reinforced ECT as effective and suggested it may be considered first-line in certain cases; it also identified rTMS and tDCS as promising, although high-quality RCTs are required.
Treatment — antipsychotics
- Use should be carefully considered. Some authors recommend avoiding them altogether in catatonia.
- There are reports of successful treatment with clozapine and other SGAs such as olanzapine, aripiprazole, risperidone and ziprasidone (particularly in catatonic schizophrenia).
- Case reports describe antipsychotic + benzodiazepine combination working when each had failed individually.
- Take account of the patient's history, psychiatric diagnosis and previous response to antipsychotics.
Stupor in a patient already on an antipsychotic: any treatment with antipsychotic medication should be avoided if there are any signs or symptoms of NMS.
Stupor from non-adherence (NMS ruled out): early re-establishment of antipsychotic medication is recommended, with consideration of adjunctive benzodiazepines — particularly relevant when catatonic symptoms follow discontinuation of clozapine.
- Catatonia has also been reported after withdrawal of long-term benzodiazepine treatment.
- When a physical health condition is associated with a catatonia-like picture, treat the underlying medical condition (e.g. lupus).
- The 2023 British Association for Psychopharmacology consensus guideline includes a more detailed referenced algorithm.
Figure 1.4 — Algorithm for treating catatonic stupor
Exclude or treat underlying physical illness
Stupor in the context of affective/conversion disorder
Lorazepam up to 4 mg/day*
Start with 2 mg and give a further 2 mg if no effect after 3 hours. Use IM route subsequently.
Start with 2 mg and give a further 2 mg if no effect after 3 hours. Use IM route subsequently.
No response after 1–2 days
Lorazepam** high dose
8–24 mg/day
8–24 mg/day
No response after 1–2 days
ECT†
Stupor in the context of psychotic illness
Rule out NMS
If NMS possible → go to the lorazepam pathway (left)
If NMS possible → go to the lorazepam pathway (left)
NMS ruled out / not taking antipsychotic medication
Consider SGA‡ e.g. clozapine, olanzapine
Some authorities recommend co-therapy with benzodiazepines
Some authorities recommend co-therapy with benzodiazepines
No response after 1–2 days
Follow the benzodiazepine/ECT protocol (left)
* Lorazepam is absorbed sublingually and is tasteless. This route may be preferred in non-cooperative patients or those who cannot swallow.
** Intravenous diazepam or lorazepam may be considered here.
† Do not wait to give ECT if there is significant danger to life.
‡ There is considerable uncertainty about antipsychotics for catatonic stupor. Antipsychotics can induce catatonia, and the risk of NMS in catatonic schizophrenia is much higher than in non-catatonic schizophrenia. An alternative approach is to use antipsychotic medication once catatonia has resolved, or when benzodiazepines or ECT have failed and there is clear evidence of a psychotic illness.
Table 1.34 — Non-benzodiazepine medications reported for catatonia/stupor
Listed alphabetically — no ranking or judgement is implied by the order.
| Antipsychotic medications | aripiprazoleclozapineolanzapinerisperidoneziprasidone |
|---|---|
| Experimental treatments* | amantadineamitriptylinecarbamazepinefluoxetinefluvoxaminelithiummemantinemethylphenidatemirtazapinetramadolvalproatezolpidem |
* Always read the primary literature before using any of the medications listed in this section.