Neuroleptic malignant syndrome

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 4 Jun 2025

Last updated: 20 Mar 2025

Neuroleptic malignant syndrome (NMS) is a potentially life-threatening complication of treatment with antipsychotic drugs, or abrupt withdrawal of dopamine agonists.

Characterized by a tetrad of altered mental status, muscle rigidity, autonomic instability, and hyperthermia.

A diagnosis of exclusion. Common differential diagnoses are sepsis and drug reactions.

NMS is a medical emergency. Treatment consists of immediate cessation of the offending medication (or resumption of the dopamine agonist) and provision of supportive measures (hydration and cooling). 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 an NMS episode.

Documenting this reaction in the medical records is important.

Definition

NMS is an uncommon, idiosyncratic, life-threatening complication of treatment with antipsychotic medications. NMS has also been associated with use of other psychotropic agents that block central dopamine pathways (e.g., metoclopramide) and with abrupt cessation of dopamine agonists. It is characterized by altered mental state, increased muscle tone or frank rigidity, dysregulated autonomic nervous system, hyperactivity, and hyperthermia.[1][2][3][4] None of these signs are exclusive to this condition, and other important diagnoses (e.g., sepsis) should be excluded first.[5][6]

This topic covers the diagnosis and management of neuroleptic malignant syndrome in adults.

History and exam

Key diagnostic factors

history of exposure to antipsychotic medications
history of abrupt withdrawal of dopaminergic drugs
altered mental status
muscle rigidity
autonomic dysfunction
hyperthermia

Full details

Risk factors

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

Full details

Diagnostic tests

1st tests 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

Full details

Tests to consider

serum iron
electroencephalogram

Full details

Treatment algorithm

ACUTE

initial episode

ONGOING

recurrence

Contributors

Expert advisers

Ronald J. Gurrera, MD

Associate Professor

Harvard Medical School

Boston

Disclosures

RJG declares that he has no competing interests.

Acknowledgements

Dr Ronald J. Gurrera would like to gratefully acknowledge Dr Peter F. Buckley, a previous contributor to this topic.

Disclosures

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

Aberdeen

Disclosures

AH declares that she has no competing interests.

John Lauriello, MD

Professor and Chair

Department of Psychiatry

University of Missouri-Columbia

Columbia

Disclosures

JL declares that he has no competing interests.

Ganesh Gopalakrishna, MD

Assistant Professor

Department of Psychiatry

University of Missouri-Columbia

Columbia

Disclosures

GG declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed, text revision (DSM-5-TR). Washington, DC: American Psychiatric Association; 2022.

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Sepsis
- Status epilepticus
- Drug misuse/overdose
More Differentials
Patient information
Neuroleptic malignant syndrome
More Patient information
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Neuroleptic malignant syndrome

Summary

Definition

History and exam

Key diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

initial episode

recurrence

Contributors

Expert advisers

Ronald J. Gurrera, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Alison Haddow, MBBS

Disclosures

John Lauriello, MD

Disclosures

Ganesh Gopalakrishna, MD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice