Neuroleptic Malignant Syndrome

Ann Pharmacother. 2016 Nov;50(11):973-981. doi: 10.1177/1060028016657553. Epub 2016 Jul 19.


Objective: To review evidence for the treatment of neuroleptic malignant syndrome (NMS) and to discuss how to rechallenge patients with neuroleptics when continued pharmacotherapy for chronic psychological illness is required.

Data sources: A PubMed search was conducted through March 2016 using available medical subject heading (MeSH) terms and keywords that included neuroleptic malignant syndrome, treatment, dantrolene, and bromocriptine. A manual search of article reference sections followed.

Study selection and data extraction: Case reports and case series in English that discussed NMS and atypical NMS treatment as well as neuroleptic rechallenge were included for review.

Data synthesis: The reported incidence of NMS was 0.02% to 0.03%, with a mortality rate of 5.6%. Current literature on NMS is primarily retrospective and emphasizes diagnostic criteria, causative agents, and potential pharmacotherapy. Details regarding timing of administration, dose, and duration of pharmacotherapy are inconsistently reported. Reported dosing strategies and outcomes have been summarized. Instances of rechallenge were infrequently reported but demonstrate that recurrence may happen at any time after NMS resolution. Recommendations regarding safe rechallenge are provided.

Conclusion: NMS is a rare adverse drug reaction, with a complex pathophysiology and presentation. Timely diagnosis and discontinuation of antipsychotic therapy is the first-line treatment, followed by supportive care and pharmacotherapy. Antipsychotic rechallenge is often required and should be attempted only after a drug-free period and with a different agent, slowly titrated with close monitoring.

Keywords: adverse drug reactions; critical care; management; neuroleptics; neuropharmacology; withdrawal.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Dantrolene / therapeutic use
  • Diagnosis, Differential
  • Humans
  • Mental Disorders / drug therapy*
  • Neuroleptic Malignant Syndrome / diagnosis
  • Neuroleptic Malignant Syndrome / etiology
  • Neuroleptic Malignant Syndrome / therapy*
  • Recurrence


  • Antipsychotic Agents
  • Dantrolene