Neuroleptic malignant syndrome

Last reviewed: 29 Aug 2022
Last updated: 11 Mar 2020



History and exam

Key diagnostic factors

  • history of exposure to antipsychotic medications
  • history of abrupt withdrawal of dopaminergic drugs
  • history of structural brain abnormality
  • altered mental status
  • muscle rigidity
  • autonomic dysfunction
  • hyperthermia
  • psychiatric history
More key diagnostic factors

Other diagnostic factors

  • history of iron deficiency
  • history of Wilson disease
Other diagnostic factors

Risk factors

  • exposure to antipsychotic medications
  • abrupt withdrawal of dopaminergic drugs
  • structural brain abnormality
  • older age
  • preexisting agitation
  • akathisia
  • male sex
  • iron deficiency
  • catatonia
  • preexisting dehydration
  • exposure to dopamine antagonists and other antipsychotics
More risk factors

Diagnostic investigations

1st investigations to order

  • CBC
  • serum creatine kinase
  • basic metabolic panel
  • brain CT scan
  • brain MRI
  • myoglobin levels and urinalysis
  • urine culture
  • blood culture
  • lumbar puncture
  • toxicology screen
  • chest x-ray
More 1st investigations to order

Investigations to consider

  • serum iron
  • EEG
More investigations to consider

Treatment algorithm


initial episode





Ronald J. Gurrera, MD

Associate Professor

Harvard Medical School




RJG is a member of the Neuroleptic Malignant Syndrome Professional Advisory Board, and has given expert testimony in medical malpractice tort claims in which NMS was alleged. He is an author of several references cited in this topic.


Dr Ronald J. Gurrera would like to gratefully acknowledge Dr Peter F. Buckley, a previous contributor to this topic. PFB is on the advisory board (a voluntary, uncompensated role) of the Neuroleptic Malignant Syndrome Information Service. He is also a consultant to Janssen Pharmaceutica and the National Institute of Mental Health (NIMH). He is conducting or has recently conducted research with funding support from AstraZeneca, NIMH, Janssen Pharmaceutica, Pfizer, Solvay, and Wyeth. Previous consultancy and research support has been from Abbott, Alamo Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Lundbeck, Janssen Pharmaceutica, Merck, NIMH, Roche Diagnostics, Pfizer, Solvay, and Wyeth. PFB has no patents or stock in any company. He is an author of several references cited in this topic. PFB is a co-investigator on a study also involving Dr John Lauriello and Dr Daniel R. Wilson, who were reviewers for this topic.

Peer reviewers

Alison Haddow, MBBS

Consultant Psychiatrist

Honorary Senior Clinical Lecturer

Royal Cornhill Hospital




AH declares that she has no competing interests.

John Lauriello, MD

Professor and Chair

Department of Psychiatry

University of Missouri-Columbia




JL declares that he has no competing interests.

Ganesh Gopalakrishna, MD

Assistant Professor

Department of Psychiatry

University of Missouri-Columbia




GG declares that he has no competing interests.

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