Neuroleptic malignant syndrome

Med Clin North Am. 1993 Jan;77(1):185-202. doi: 10.1016/s0025-7125(16)30278-4.


Neuroleptic malignant syndrome is a rare but potentially fatal reaction associated with neuroleptic drugs. It occurs in about 0.2% of patients treated with neuroleptics. Risk factors include previous episodes, dehydration, agitation, and the rate and route of neuroleptic administration. Although NMS has been reported in patients with diverse psychiatric diagnoses, as well as in normal subjects, patients with organic brain disorders or mood disorders, particularly when receiving lithium, may be at increased risk. Standardized criteria for the diagnosis of NMS have been developed and emphasize the classic findings of hyperthermia, muscle rigidity, mental status changes, and autonomic dysfunction. The syndrome lasts 7 to 10 days in uncomplicated cases receiving oral neuroleptics. Treatment consists primarily of early recognition, discontinuation of triggering drugs, management of fluid balance, temperature reduction, and monitoring for complications. Use of dopamine agonists or dantrolene or both should be considered and may be indicated in more severe, prolonged, or refractory cases. Electroconvulsive therapy has been used successfully in some cases and is particularly useful in the post-NMS patient. As a result of these measures, mortality from NMS has declined in recent years although fatalities still occur. Neuroleptics may be safely reintroduced in the management of the majority of patients recovered from an NMS episode, although a significant risk of recurrence does exist, dependent in part on time elapsed since recovery and dose or potency of neuroleptics used. Data drawn from clinical observations and basic studies support the primary role of an acute reduction in brain dopamine activity in the development of NMS. Additional studies of facilitating cofactors may lead to innovative risk-reduction strategies and the development of safer neuroleptic drugs.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Antipsychotic Agents / adverse effects*
  • Dantrolene / therapeutic use
  • Diagnosis, Differential
  • Dopamine Agents / therapeutic use
  • Electric Stimulation Therapy
  • Humans
  • Neuroleptic Malignant Syndrome* / diagnosis
  • Neuroleptic Malignant Syndrome* / etiology
  • Neuroleptic Malignant Syndrome* / physiopathology
  • Prognosis
  • Recurrence
  • Risk Factors
  • Sex Factors


  • Antipsychotic Agents
  • Dopamine Agents
  • Dantrolene