Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome is a topic covered in the 5-Minute Emergency Consult.

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  • Life-threatening neurologic disorder most often caused by an adverse reaction to a neuroleptic or antipsychotic medication.
  • Mortality can be as high as 20%
  • May develop any time during therapy with neuroleptics—from a few days to many years:
    • Most often occurs in the 1st mo of therapy
  • Muscular rigidity and tremor resulting from dopamine blockade in the nigrostriatal pathway
  • Hyperthermia due to central dopamine receptor blockage in the hypothalamus.
  • More likely in the setting of benzodiazepine withdrawal
  • May be indistinguishable from other causes of drug-induced hyperthermia (malignant hyperthermia, serotonin syndrome, anticholinergic toxins, or sympathomimetic poisoning)
  • Most episodes resolve within 2 wk after cessation of offending agent.
  • Diagnostic criteria:
    • Development of elevated temperature and severe muscle rigidity in association with use of antipsychotic/neuroleptic medication
    • 2 or more of the following:
      • Diaphoresis
      • Dysphagia
      • Tremor
      • Incontinence
      • Altered mental status (range from confusion to coma)
      • Mutism
      • Tachycardia
      • Elevated labile BP
      • Leukocytosis
      • Lab evidence of muscle injury
    • Symptoms are not caused by another disease process


  • Rare complication of treatment with neuroleptics:
    • Phenothiazines
      • Chlorpromazine (Thorazine)
      • Fluphenazine (Modecate)
      • Prochlorperazine (Compazine)
      • Promethazine (Phenergan)
      • Metoclopramide (Reglan)
    • Butyrophenones
      • Haloperidol
      • Droperidol
    • Atypical antipsychotics
      • Risperidone (Risperdal)
      • Olanzapine (Zyprexa)
      • Quetiapine (Seroquel)
      • Clozapine (Clozaril)
      • Aripiprazole (Abilify)
  • Occurs in ∼1% of patients treated with neuroleptics (especially haloperidol)
  • Has also been associated with abrupt withdrawal from dopamine agonists in Parkinson disease
  • SSRIs or lithium along with neuroleptic medication may be associated with an increased risk
  • Risk factors:
    • Rapid drug loading
    • High-dose antipsychotics
    • High-potency antipsychotics
    • IV administration of drug
    • Dehydration
    • Prior neuroleptic malignant syndrome (NMS)
    • Preceding extreme psychomotor agitation or catatonia
    • Infection or surgery

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