Neuroleptic malignant syndrome (NMS) is a life-threatening complication of treatment with dopamine antagonists, or occasionally abrupt withdrawal of dopamine agonists.
It is characterised by hyperthermia, muscle rigidity, altered mental status, sympathetic nervous system lability, and hypermetabolism, as well as elevated creatine kinase.
Other causes should be excluded before a diagnosis of NMS is made. Common differential diagnoses are sepsis and drug reactions.
NMS is a medical emergency. Treatment consists of immediate cessation of the dopamine antagonist (or restarting or continuing of the dopamine agonist) and supportive measures (rehydration, cooling, and treatment of rhabdomyolysis if present). Additional treatment may be considered if supportive interventions fail.
A delay of at least 2 weeks in restarting antipsychotic treatment is advised following full resolution of NMS.
Documenting this reaction in the medical records is important.
NMS is an uncommon, idiosyncratic, life-threatening complication of treatment with dopamine antagonists. NMS has also been associated with other agents that block central dopamine pathways (e.g., metoclopramide).
This topic covers the diagnosis and management of neuroleptic malignant syndrome in adults.
History and exam
Key diagnostic factors
- presence of risk factors
- muscle rigidity
- altered mental status
- sympathetic nervous system lability
- exposure to antipsychotic medications
- structural brain abnormality
- abrupt withdrawal of dopaminergic drugs
- older age
- pre-existing agitation
- male sex
- iron deficiency
- pre-existing dehydration
- exposure to other dopamine antagonists
1st investigations to order
- serum creatine kinase (CK)
- blood gas
- blood glucose
- urea, electrolytes, and creatinine
- liver function tests
- clotting screen
- myoglobin levels and urinalysis
Investigations to consider
- brain CT scan
- urine culture
- blood culture
- chest x-ray
- toxicology screen
- lumbar puncture
- serum iron
after resolution of NMS
Jonathan Mitchell, MBChB, MRCPsych
Sheffield Health and Social Care NHS Foundation Trust
JM declares that he has no competing interests.
Melvyn Jenkins-Welch, BSc(Hons), MBBS, MSc, FRCA, FFICM
Consultant Critical Care Medicine
Cardiff and Vale ULHB
MJW declares that he has no competing interests.
BMJ Best Practice would like to gratefully acknowledge the previous expert contributor, whose work has been retained in parts of the content:
Ronald J. Gurrera, MD
Harvard Medical School
Disclosures: 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.
Nigel Langford, MD, MRCP, MRPharmS
Consultant Physician in Clinical Pharmacology and Therapeutics/Acute and General Internal Medicine
Leicester Royal Infirmary
Honorary Senior Lecturer
University of Leicester
NL has worked as a clinical pharmacologist expert witness at criminal, civil, family and coroners courts; given lectures, published articles, and written book chapters.
Section Editor and Comorbidities Editor, BMJ Best Practice
AS declares that she has no competing interests.
Lead Section Editor, BMJ Best Practice
TAO declares that she has no competing interests.
Drug Editor, BMJ Best Practice
AM declares that he has no competing interests.
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