Catatonia, NMS and serotonin syndrome

• Catatonia is a potentially fatal neuropsychiatric syndrome of altered movement, speech and behaviour that occurs with psychiatric, neurological and medical illness. It is diagnosed by the presence of three or more catatonic signs. ^[1]
• The nearest mimics that a clinician must never miss are neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS). Both present with fever, rigidity and altered consciousness, but they are triggered by different drugs and managed differently.
• Malignant (lethal) catatonia is the severe form of catatonia with autonomic dysfunction and hyperthermia; NMS is often classified as an antipsychotic-induced subtype of it.
• First-line treatment of catatonia is a benzodiazepine, most often lorazepam. The lorazepam challenge uses 1 to 2 mg and a positive response is roughly a 50% fall in catatonic signs.
• Management of all three is supportive first, then syndrome-specific drugs: benzodiazepines, ECT and removal of trigger drugs; dantrolene for extreme hyperthermia in NMS or malignant hyperthermia.
• Malignant hyperthermia (MH) is a separate anesthetic emergency. It is not a poisoning and is treated with dantrolene.

By the end of this page you should be able to:

1. Define catatonia, NMS, serotonin syndrome and malignant hyperthermia, and state the diagnostic threshold for catatonia. ^[8]
2. Recognise the clinical signs of catatonia and perform a lorazepam challenge with the correct dose, timing and end point. ^[1]
3. Distinguish NMS from serotonin syndrome and malignant hyperthermia on clinical grounds, including onset, neuromuscular findings and trigger.
4. Choose and justify first-line and second-line treatment for each syndrome, with doses, route and duration.
5. State the main complications, prognosis and special-group considerations, including in pregnancy and low-resource settings.
6. Explain the relationship between catatonia, malignant catatonia and NMS, and why this remains debated.

The earlier view that catatonia was simply a subtype of schizophrenia has been abandoned. Both ICD-11 and DSM-5-TR recognise catatonia across many conditions, and the syndromal concept is now standard. ^[1][3] A clinical diagnosis is made on the presence of three or more of more than 50 described catatonic signs (including stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerisms, stereotypy, agitation and echophenomena). ^[1] The wording here is paraphrased, since DSM-5-TR and ICD-11 wording is copyrighted.

Important classification points:

• Malignant hyperthermia is not a medication toxidrome. It does not occur with antipsychotics or antidepressants. It belongs to anaesthetic safety.
• Serotonin syndrome is not catatonia. Although some authors have argued that SS is a form of catatonia, there is currently insufficient systematic evidence to support this. ^[1]
• NMS versus malignant catatonia. The two are clinically very hard to tell apart. Many authors regard NMS as an antipsychotic-induced subtype of malignant catatonia; others regard them as distinct. ^[1]

Catatonia is commoner than many clinicians realise. A meta-analysis found that roughly 9% (95% CI 6.9 to 11.7%) of patients seen in mental health services have catatonic features; in series with more than 1000 patients the figure falls to 2.3% (95% CI 1.3 to 3.9%), probably because small studies used systematic detection. In the general population, incidence in London was estimated at 10.6 cases per 100 000 person-years, and in US general hospitals a discharge diagnosis of catatonia occurred in 0.05% of admissions. ^[1] Catatonia is under-diagnosed clinically.

NMS is now rare: 0.02 to 0.03% of patients given dopamine antagonists, down from 1 to 3% reported in the 1980s. Mortality has fallen to under 10% in BAP guidance; one 2015 NMS review gives about 10%, summarising different case series. ^[1][4][7] About two-thirds of cases develop within the first 1 to 2 weeks after a drug is started. ^[1]

Serotonin syndrome has no reliable population incidence. It is under-recognised and mild cases are often self-limiting. Moderate serotonin syndrome occurs in roughly 15% of SSRI poisonings. ^[8] SSRI exposures reported to US poison control rose substantially between 2002 and 2016. ^[8]

Malignant hyperthermia occurs in 0.18 to 3.9 cases per 100 000 general anaesthetics. More than half of reported cases are under 18 years of age and the condition is about three times more common in males. Mortality fell from 70 to 80% in the 1960s to 0 to 18.2% by 2010, and to 10% or less when dantrolene is used. ^[9]

Catatonia is a final common presentation, not a single disease. Psychiatric associations (DSM-5-TR specifier) include depressive episodes, bipolar disorder, schizophrenia and other psychoses, autism spectrum disorder and unspecified catatonia. ^[1][11] Medical causes make up a large minority of cases, particularly neurological and inflammatory brain disease. ^[1] The commonest medical contributors in one systematic review of 302 patients were inflammatory brain disorders (28.8%), especially encephalitis, followed by neural injury (19.2%), medicines or toxins (11.6%, including benzodiazepine withdrawal), structural brain lesions (9.6%) and epilepsy (9.3%). ^[1] Triggers and associations to check for include: ^[10]

• Mood or psychotic disorders, especially mania and depression.
• Neurological disease, structural brain lesions, epilepsy, autoimmune or infectious encephalitis.
• Medicines: antipsychotics (including as a precipitant), baclofen, corticosteroids, disulfiram, ketamine, ciclosporin, beta-lactams and many others; drug withdrawal (benzodiazepines, alcohol, clozapine, zolpidem).
• Systemic illness: sepsis, metabolic disturbance, renal failure, post-operative states, especially in older adults.

A collateral history, prior catatonia and any prior NMS should be asked about in every case. ^[1]

Trigger: dopamine (D2) receptor blockade, almost always from an antipsychotic, with high-affinity typical agents such as haloperidol and fluphenazine carrying the greatest risk. Second-generation agents can also cause NMS, sometimes in an atypical form with milder or absent rigidity or fever. Dopamine-depleting or dopamine-blocking antiemetics, and rapid withdrawal of a dopaminergic drug, can also precipitate it. ^[4][7][1] Most cases begin within 1 to 2 weeks of drug initiation. ^[1] First-generation agents carry a greater risk of poor outcomes when antipsychotics are given during catatonia. ^[10]

Trigger: any net increase in central serotonergic tone. Common precipitants include monoamine oxidase inhibitors (MAOIs) with serotonergic drugs; SSRIs or SNRIs with tramadol, fentanyl, ondansetron, linezolid, methylene blue or triptans; and overdoses. MAOI combinations are the most dangerous. ^[8] Many severe cases occur at therapeutic doses rather than only in overdose, and cytochrome P450 interactions (for example SSRIs with tramadol or fluconazole) are common contributors. ^[8]

Trigger: volatile anaesthetics (including sevoflurane and desflurane) or succinylcholine in a genetically susceptible person, in whom calcium release from skeletal muscle sarcoplasmic reticulum is abnormally accelerated. Sedatives and opioids are safe. ^[9]

Catatonia is not fully explained, but brain GABA imaging shows reduced GABA-A receptor binding in frontal and parietal cortex, and lorazepam normalises orbitofrontal-prefrontal activity. ^[1] Glutamate, dopamine and NMDA receptor effects are implicated. The clinical picture reflects a disorder of initiation and inhibition rather than weakness.

NMS is believed to result from sudden dopamine receptor blockade in the striatum, producing extrapyramidal rigidity and thermogenesis, and possibly in the hypothalamus, altering temperature control. Some authors view it as an antipsychotic-induced variant of malignant catatonia. ^[1][4]

In serotonin syndrome, receptor overstimulation, predominantly 5-HT1A and 5-HT2A, produces clonus, hyperreflexia, hyperpyrexia and autonomic instability. It is dose-dependent and usually develops over hours. ^[8]

Malignant hyperthermia is caused by excessive calcium release from the sarcoplasmic reticulum in skeletal muscle, producing sustained contraction, hypermetabolism, heat and rhabdomyolysis. Dantrolene blocks the ryanodine receptor and stops this calcium release. ^[9]

The picture varies between retarded (stuporous) and excited forms, and remits or fluctuates. Major groups of signs: ^[1]

• Stupor, immobility, withdrawal and reduced oral intake.
• Catalepsy, waxy flexibility, posturing, mannerisms and stereotypies.
• Negativism, automatic obedience, echolalia and echopraxia.
• Mutism, verbigeration, reduced speech.
• Ambitendency.
• Affective blunting, staring, anxiety and agitation.
• Autonomic abnormalities (tachycardia, hypertension, fever).

Many patients with retarded catatonia still understand what is said to them and later recall it; this helps avoid mistaking catatonia for voluntary non-cooperation. ^[1]

Classic characteristics: mental status changes, fever, muscle rigidity and autonomic instability. ^[4] Other common features include dysphagia, drooling, tremor, tachycardia, labile blood pressure, diaphoresis, leukocytosis, elevated creatine kinase and low serum iron. ^[1][7] Onset is typically over days. Common precipitants are a recent antipsychotic combined with agitation, dehydration or medical illness.

The classic triad is altered mental status (anxiety, agitation, confusion), autonomic overactivity (sweating, tachycardia, hypertension, mydriasis, vomiting, diarrhoea) and neuromuscular hyperactivity (tremor, myoclonus, hyperreflexia, clonus, rigidity). ^[8] Clonus is usually more prominent in the lower limbs. Onset is rapid: more than 60% present within 6 hours and most within 24 hours, though about a quarter present after 24 hours when drugs are titrated gradually. ^[8] Severe cases include temperature above 41.1 degrees C, delirium, hyperactive bowel sounds and haemodynamic instability. ^[8]

Within minutes of exposure: unexplained hypercarbia (end-tidal CO2 above 55 mm Hg), tachycardia, masseter rigidity, temperature increase above 0.5 degree C in 15 minutes, often exceeding 40 degrees C, then metabolic acidosis, peaked T waves, myoglobinuria and possible cardiac arrest. ^[9]

Three conditions (NMS, SS, MH) are easy to confuse with catatonia itself. The table compares the four; where the literature disagrees, the disagreement is stated.

Cross-check with emergency medicine: in poisoned patients, serotonin syndrome and NMS are recognised as hyperthermic toxidromes alongside cholinergic, anticholinergic and sympathomimetic presentations. Malignant hyperthermia is not a poisoning toxidrome; it is a pharmacogenetic anaesthetic emergency, and an overdose of an illicit sympathomimetic can masquerade as either syndrome. ^[6][8]

There is no laboratory test that diagnoses catatonia. ^[3]

• Rating scale: Bush-Francis Catatonia Rating Scale (BFCRS) or similar, used serially. ^[1]
• Severity cut-off: a BFCRS score under 7 suggests low suspicion and over 20 high suspicion in the recent lorazepam challenge algorithm. ^[2]
• Basic workup for every first episode: blood count, electrolytes, renal and liver function, thyroid function, creatine kinase, glucose, calcium, infection markers, urinalysis, EEG if epilepsy is possible, and neuroimaging to exclude structural or inflammatory brain disease. ^[1]
• Serum iron: low iron has been reported to predict a poor benzodiazepine response. ^[1]
• Lorazepam challenge: diagnostic and predictive; see below.

• Creatine kinase usually markedly raised; leukocytosis; low serum iron. ^[1][7]
• ECG, renal function and myoglobinuria to detect rhabdomyolysis and renal failure. ^[1]

• No diagnostic test. Diagnosis is clinical, using a classification system; the Hunter Serotonin Toxicity Criteria are the commonest. ^[5][8]
• Laboratory tests are non-specific but needed to exclude infection, electrolyte disturbance or rhabdomyolysis. Creatinine, creatine kinase, liver enzymes and arterial blood gas may be abnormal in severe cases. ^[8]

• Clinical diagnosis during anaesthesia: rising end-tidal CO2, tachycardia, rigidity, fever. ^[9]
• Arterial blood gas, electrolytes, CK afterwards. Muscle biopsy and genetic testing (RYR1 and others) confirm susceptibility but are not definitive in every case. ^[9]

Catatonia should be diagnosed on the presence of three or more catatonic signs, as in DSM-5-TR or ICD-11. ^[1][11] A threshold of three gives the best balance of sensitivity and specificity in studies; four is more specific but misses cases. ^[1]

• Mild: normothermic, mild autonomic signs and neuromuscular signs (tremor, mild clonus). ^[8]
• Moderate: temperature above 40 degrees C, ocular clonus, agitation, pressured speech, hypervigilance, mydriasis. ^[8]
• Severe: temperature above 41.1 degrees C, autonomic instability, delirium, muscle rigidity, hyperactive bowel sounds, rhabdomyolysis, DIC, acute respiratory distress. ^[8]

• Mild, early: mild rigidity, confusion, temperature under 38 degrees C, heart rate under 100. ^[1]
• Moderate: moderate rigidity, temperature 38 to 40 degrees C with prominent parkinsonism. ^[1]
• Severe: extreme hyperthermia over 40 degrees C with severe rigidity. ^[1]

Marked autonomic instability with hyperthermia, typically in addition to ordinary catatonic signs; mortality around 10% in modern reports, down from over 75% in the pre-antipsychotic era. ^[1]

This is the single most useful bedside test in catatonia. ^[1]

1. Examine and score the patient with a standardised instrument (for example BFCRS) at baseline.
2. Give lorazepam 1 to 2 mg intravenously, or 1 to 2 mg intramuscularly, or 2 mg orally. ^[1]
3. Re-assess after 5 minutes (IV), 15 minutes (IM) or 30 minutes (oral). ^[1]
4. A positive response is a 50% reduction in score. Clinical experience allows leeway where there is clear change in more than one symptom domain even if below 50%. ^[1][2]
5. If no response, a further challenge (preferably parenteral) may be given and the patient re-assessed. ^[1]
6. Do not stop after one dose in a high-suspicion case. Repeat 2 mg IV after 1 to 2 hours if needed (shorter intervals risk oversedation and make interpretation hard). If still no improvement, schedule lorazepam 2 to 4 mg IV every 6 to 8 hours for at least 24 to 48 hours as an extended challenge. In malignant catatonia the schedule runs faster, with doses 15 to 30 minutes apart, in critical care, with ECT at hand. ^{[2] [1]}

A positive challenge supports the diagnosis but is not 100% specific (stiff person syndrome and non-convulsive status epilepticus also improve). It is also a useful predictor of later benzodiazepine response. ^[1]

Oral zolpidem 10 mg (or 5 mg in older patients) can be used as an alternative diagnostic and therapeutic challenge, with onset of 10 to 30 minutes and effect for 3 to 6 hours. It needs no IV line but is less practical when the patient cannot swallow. ^[1]

Treat as soon as possible after recognition; it is not always necessary to wait for all investigations. ^[1] Two strands run together: specific treatment for the catatonia, and treatment of the underlying disorder. ^[1] Complications must be prevented and managed (pressure ulcers, contractures, DVT, dehydration, infection). ^[1]

First-line is a trial of benzodiazepines and/or ECT, with response rates of 66 to 100% in Western benzodiazepine studies (Asian study results are lower, possibly for storage reasons) and 59 to 100% for ECT. ^[1] The choice between them weighs side effects, whether ECT will treat the underlying condition (depression or mania), availability and consent. Where benzodiazepines fail, use ECT. ^[1]

Benzodiazepine practicalities

• Lorazepam is the preferred agent, in oral, sublingual, intramuscular or IV form. Parenteral forms help when negativism prevents oral dosing. ^[1]
• Doses are usually 1 to 4 mg per day at the start, rising up to 16 mg per day, and in some cases 24 mg per day. ^[1]
• An adequate trial is complete when catatonia is treated, titration stops because of side effects, or the dose reaches at least 16 mg per day. ^[1]
• Lorazepam should not be stopped abruptly but tapered; if the syndrome returns on withdrawal, treat the underlying cause and taper more slowly. ^[1]

ECT: bilateral ECT, at least twice weekly in acute catatonia, 3 to 35 sessions in the literature (mean 9), with number guided by response. ^[1]

Special efficacy notes

• Clozapine withdrawal catatonia: restart clozapine (and ECT if needed); benzodiazepines are less effective. ^[1]
• Benzodiazepine withdrawal catatonia: restart a benzodiazepine. ^[1]
• Chronic, mild catatonia in schizophrenia: benzodiazepines and ECT are less effective; clozapine may help. ^[1]
• Malignant catatonia and NMS: see below.

1. Discontinue all dopamine antagonists. ^[1]
2. Start lorazepam 8 mg per day orally, intramuscularly or intravenously, titrating up according to response and tolerability to a maximum of 24 mg per day. ^[1]
3. If there is partial or no response within 48 to 72 hours, institute bilateral ECT once or twice daily for up to 5 days until the syndrome abates, then three times weekly until sustained improvement; usually 5 to 20 treatments in total. ^[1]
4. ECT is apparently more effective when started early (within 5 days of onset in older series). ^[1]

1. Stop all dopamine antagonists and anticholinergics. This is the single most important step. ^[1][4]
2. Supportive care is the bedrock: secure airway and ventilation, temperature control, aggressive IV fluids, monitoring for hyperkalaemia, renal failure, rhabdomyolysis, DVT, aspiration and cardiorespiratory failure; high-dependency care if severe. ^[1]
3. Treat by severity: ^[1]
   • Mild, early (temperature under 38 degrees C, heart rate under 100): trial of lorazepam.
   • Moderate (prominent parkinsonism, temperatures 38 to 40 degrees C): bromocriptine or amantadine. ^[1]
   • Severe (extreme hyperthermia over 40 degrees C with severe rigidity): intravenous dantrolene. It should not be co-administered with calcium channel blockers (verapamil, diltiazem), because hyperkalaemia and cardiovascular collapse have occurred; amlodipine or nifedipine may be safer alternatives if needed. ^[1][9]
4. If there is no response by 2 to 3 days, a delayed response is unlikely and ECT should be considered. ECT has a mortality of about 10% in one reviewed series versus 21% with supportive care alone, and also treats the underlying condition when antipsychotics must be avoided. ^[1]
5. Patients who recover have roughly a 30% chance of recurrence after antipsychotic rechallenge. Risk reduction: minimise other risk factors (agitation, medical illness, dehydration), wait at least 2 weeks before rechallenge, use a low dose of a second-generation antipsychotic with gradual titration and careful monitoring. ^[1]

NMS itself is mostly self-limiting after the trigger is removed; recovery is reported as 7 to 10 days in BAP guidance and 3 to 14 days in the 2015 NMS review (3 to 14 days unless complications develop). ^[1][7]

1. Stop the offending serotonergic drug(s) and provide supportive care: oxygen, IV fluids, continuous temperature and cardiac monitoring. ^[8]
2. Sedate with benzodiazepines (diazepam, midazolam) to control agitation and the hyperadrenergic drive. Chemical restraint is preferred over physical restraint. ^[8]
3. Autonomic instability: short-acting agents (esmolol or nitroprusside) for labile hypertension; low-dose norepinephrine, epinephrine or phenylephrine for hypotension after MAOIs; avoid longer-acting beta-blockers such as propranolol and indirect amines such as dopamine. ^[8]
4. Hyperthermia: active cooling. Antipyretics do not work as the cause is neuromuscular, not pyrexial. ^[8]
5. Antidote: if supportive measures fail, cyproheptadine, an antihistamine with broad serotonin antagonism. Loading dose 12 mg orally or crushed via nasogastric tube, then 2 mg every 2 hours until improvement; alternatively 8 mg every 6 hours once controlled. ^[8]
6. Severe (temperature over 41.1 degrees C): immediate paralysis with a non-depolarising agent, intubation, sedation and ICU care. Succinylcholine and fentanyl should be avoided in this situation. ^[8]
7. ECT is not recommended and may worsen serotonin syndrome. ^[1]

Most cases resolve within 24 to 72 hours, longer for drugs with long half-lives or active metabolites (for example fluoxetine and its metabolite). Patients who took irreversible MAOIs can stay at risk for days. ^[8]

1. Stop the triggering anaesthetic immediately (turn off vaporiser, remove or flush circuit).
2. Hyperventilate with high-flow oxygen to clear anaesthetic and correct acidosis.
3. Dantrolene intravenously: 1 to 2 mg per kg initially, preferably 2 mg per kg over about 10 minutes; repeat every 10 minutes until CO2, temperature and rigidity improve. ^[9]
   • Guidelines differ on the initial dose: the European Malignant Hyperthermia Group recommends 2 to 2.5 mg per kg, the Japanese package insert specifies 1 mg per kg, and the JSA 2025 guideline presents an initial 1 to 2 mg per kg with a preference for 2 mg per kg. ^[9]
   • Prepare for a total dose of up to 7 mg per kg (Japanese package insert maximum) and, if still responding, over 10 mg per kg according to Western guidance. ^[9]
   • Onset of action is roughly 5 minutes and half-life 5 to 6 hours. ^[9]
4. Cooling and supportive care for complications (hyperkalaemia, acidosis, myoglobinuria, DIC). Do not combine dantrolene with calcium channel blockers. ^[9]
5. Dantrolene must be immediately available wherever triggering agents are used. ^[6]

Antipsychotics can precipitate and worsen catatonia and are themselves a risk factor for NMS. Where an underlying psychotic disorder exists, second-generation agents such as clozapine, risperidone or amisulpride are more often reported as beneficial and first-generation agents should be avoided; benzodiazepines should be continued as an adjunct and introduced first where possible. ^[1][10] A recent systematic review found antipsychotics beneficial in 60% of reported trials, neutral in 29% and harmful in 11%, most harm occurring with first-generation agents. ^[10] The Maudsley prescribing guidelines suggest careful consideration of olanzapine or clozapine in schizophrenic catatonia once NMS has been excluded. ^[10] Antipsychotics should be withdrawn whenever malignant catatonia or NMS is suspected. ^[1]

Catatonia carries a serious medical burden, especially when prolonged: infections (pneumonia, urinary tract infection, sepsis), rhabdomyolysis, dehydration, deep vein thrombosis, pulmonary embolism, urinary retention, pressure ulcers, renal failure, cardiac arrhythmia, NMS and hypernatraemia. ^[1] Recommendations include thromboprophylaxis, pressure area care, stretching, nutrition and hydration. ^[1]

NMS and severe serotonin syndrome also risk renal failure, rhabdomyolysis, DIC, aspiration pneumonia, seizures and death. ^[1][8] MH risks hyperkalaemia, myoglobinuric renal failure, DIC and death. ^[9]

• Catatonia: prognosis is good with early, aggressive treatment; response is more likely and faster when treatment is started early. ^[1] With benzodiazepines and ECT, reported response ranges from 66 to 100% in Western studies. ^[1]
• Malignant catatonia: modern mortality around 10% (down from over 75%). ^[1]
• NMS: recovery is reported as 7 to 10 days with discontinuation of the drug and good supportive care in BAP guidance (3 to 14 days in the 2015 NMS review), and modern mortality is under 10% (BAP) or about 10% (2015 NMS review). ^[1][7]
• Serotonin syndrome: most cases resolve within 24 to 72 hours; prognosis is good if recognised early and the drug stopped. ^[8]
• Malignant hyperthermia: mortality fell from 70 to 80% in the 1960s to 0 to 18% by 2010, and to 10% or less with dantrolene. ^[9]

• Think catatonia in any patient with a markedly altered level of activity or abnormal behaviour, including in medical, surgical and ICU settings. ^[1]
• Prevent recurrence by ensuring the underlying disorder is adequately treated and the benzodiazepine is tapered rather than stopped abruptly. ^[1]
• For NMS prevention, use the lowest effective dose, titrate slowly, monitor for early signs and avoid dehydration and agitation during antipsychotic use. ^[1]
• For SS prevention, avoid combining serotonergic agents, warn patients about over-the-counter and herbal serotonergics, and review interactions when prescribing. ^[8]
• For MH prevention, take a family and anaesthetic history and use non-triggering agents in patients with known or suspected susceptibility; dantrolene must be on hand where triggers are used. ^[6][9]
• Screening or genetics for malignant hyperthermia is not routine; diagnosis is clinical with biopsy and genetic testing after the event. ^[9]

• Catatonia also occurs in children and adolescents, particularly with neurodevelopmental conditions including autism. Diagnosis requires a marked change from baseline and treatment follows the same principles, with benzodiazepines and ECT available. ^[1]
• Malignant hyperthermia is more common under 18 years. ^[9]

• In pregnancy, where catatonia is severe and risks are high, start lorazepam up to 4 mg per day; if ineffective, consider ECT. ^[1]
• If lorazepam is used above 4 mg per day, the mother should not breastfeed. Women may breastfeed after ECT. ^[1]
• NMS in pregnancy requires the same supportive and dopamine-directed approach. ^[1][4]

• A medical cause contributes to catatonia in almost 80% of older patients, so the medical workup (including delirium, infection and metabolic disturbance) is particularly important. ^[1]
• Benzodiazepines may cause sedation; use lower starting doses and monitor for falls. ^[1]

Catatonia occurs at elevated rates in autism; diagnosis is often hardest here because of overlap with baseline traits, and treatment uses benzodiazepines and ECT where appropriate. ^[1]

• Keep the diagnostic threshold in mind: three or more signs. A benzodiazepine response is supportive even without a rating scale.
• Lorazepam 1 to 2 mg can usually be given by intravenous or intramuscular injection where available; where it is not available, other benzodiazepines may be used, but lorazepam is preferred. ^[1]
• Without ECT, malignant and treatment-resistant catatonia is dangerous; early transfer should be arranged where possible. ^[1]
• For NMS and serotonin syndrome, the essentials are stopping the trigger drug and providing supportive care. Neither dantrolene nor cyproheptadine can be assumed to be available; active cooling, sedation with whatever benzodiazepine is available and fluids save lives. ^[1][8]
• For malignant hyperthermia, dantrolene must be stocked wherever halogenated anaesthetics or succinylcholine are used, with compatible distilled water for reconstitution. ^[9]

• Catatonia is diagnosed by three or more of over 50 catatonic signs and presents across psychiatric and medical illness, not only schizophrenia.
• First-line treatment is a benzodiazepine (usually lorazepam), with a challenge of 1 to 2 mg and a response defined as around 50% reduction in catatonic signs.
• An adequate trial is pushed to at least 16 mg per day of lorazepam or until response or side effects; higher (up to 24 mg) is sometimes needed.
• Malignant catatonia is treated with lorazepam 8 mg per day rising to 24 mg, then bilateral ECT if no improvement within 48 to 72 hours. ^[1]
• NMS (prevalence 0.02 to 0.03%, mortality under 10%) is managed by stopping dopamine antagonists, good supportive care, then lorazepam if mild, bromocriptine or amantadine if moderate and dantrolene with extreme hyperthermia; ECT if no response in 2 to 3 days. ^[1]
• Serotonin syndrome is triggered by serotonergic drugs and managed by stopping the drug, supportive care, benzodiazepines, active cooling and cyproheptadine (12 mg then 2 mg every 2 hours); paralysis and intubation above 41.1 degrees C; ECT is not useful.
• Distinguish SS (excess neuromuscular activity, clonus, diarrhoea) from NMS (lead-pipe rigidity, reduced activity), and both from malignant hyperthermia (anaesthetic trigger, minutes).
• MH is treated with dantrolene 1 to 2 mg per kg IV (preferably 2 mg per kg), repeated every 10 minutes up to 7 to 10 mg per kg, with hyperventilation and cooling.
• ECT works for catatonia, malignant catatonia and NMS, but not for serotonin syndrome.

• Emergency medicine: toxidromes and approach to the poisoned patient (plain text) is the natural companion for the toxidrome cross-check in this page.
• Psychiatry: management of schizophrenia, bipolar disorder, major depression, obsessive-compulsive disorder, delirium and movement disorders (plain text).
• Anaesthesia: perioperative care and malignant hyperthermia (plain text).