Neuroleptic malignant syndrome (NMS) is a life-threatening adverse drug reaction to dopamine antagonists
The condition is characterized by rigidity, altered mental status, hyperthermia and autonomic dysfunction (i.e., diaphoresis, tachycardia, tachypnea and labile blood pressure).1 It occurs in about 0.02%–0.03% of patients who receive antipsychotic medications, with mortality as high as 5.6% based on recent estimates.2 It can also be caused by dopamine-antagonist antiemetics (e.g., metoclopramide).2,3
Symptoms typically begin between several days and 2 weeks after starting the drug or changing its dose
The creatine kinase level is often greater than 1000 IU/L.1,3 Brain imaging, lumbar puncture, metabolic testing and drug immunoassays can be considered to exclude alternate causes (e.g., toxic, metabolic, infectious, structural).1,2 A thorough medication history helps distinguish NMS from sympathomimetic or anticholinergic toxicity and serotonin syndrome.2,4
The condition can develop at any antipsychotic dose and most cases occur at therapeutic doses
Risk factors include use of high-potency first-generation antipsychotic agents (i.e., haloperidol, fluphenazine), high doses, rapid dose escalation, parenteral formulations and history of NMS. Patients on stable doses may develop NMS during acute illness.2–5
Management involves stopping the culprit drug and aggressive supportive care
Patients may require an intensive care setting to provide volume resuscitation, treat hyperthermia and manage end-organ dysfunction.3,5 Benzodiazepines (i.e., intramuscular or intravenous lorazepam 1–2 mg every 4–6 h) are first-line treatments for muscle rigidity and sympathetic overactivity, including agitation and hyperthermia.3,5 Cooling blankets and ice packs should also be used for hyperthermia. The efficacy of dantrolene, dopamine agonists such as bromocriptine, and electroconvulsive therapy is not well established. These may be considered for worsening symptoms despite initial treatment, with guidance on doses for pharmacotherapy provided by the local poison centre. Venous thromboprophylaxis should be considered in all patients.4
Symptoms typically resolve 7–10 days after stopping the drug
When recognized and treated early, most patients recover completely.5 If ongoing use of antipsychotic medications is warranted, measures to decrease risk of recurrence (estimated at 10%–30%) include reinitiation at least 2 weeks after symptom resolution (4 wk for depot injections), use of low-potency antipsychotic agents, low doses and slow uptitration.2–5
Footnotes
Competing interests: None declared.
This article has been peer reviewed.
References
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