Serotonin syndrome

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

Last reviewed: 6 Sep 2025

Last updated: 07 Oct 2022

Serotonin syndrome is the clinical manifestation of excess serotonin in the central nervous system, resulting from the therapeutic use or overdose of serotonergic drugs.

Characterized by a triad of clinical features: neuromuscular excitation, autonomic effects, and altered mental status.

Better described as a spectrum of toxicity, ranging from mild to severe, rather than a "syndrome".

Diagnosis is clinical and should be based on the Hunter Serotonin Toxicity Criteria (HSTC), of which clonus is a key diagnostic feature.

Treatment is guided by the severity of toxicity and involves cessation of the drug(s), supportive care, and antiserotonergic drugs in select patients.

Definition

An excess of synaptic serotonin in the CNS that clinically manifests as the triad of neuromuscular excitation, autonomic effects, and altered mental status.[1] Can result from therapeutic use of medications, drug overdose, or specific drug-drug interactions. It is better described as a spectrum of toxicity rather than a specific syndrome.[2][3] Commonly known as serotonin toxicity.

History and exam

Key diagnostic factors

exposure to a serotonergic drug
clonus
hyperreflexia

Full details

Other diagnostic factors

anxiety
agitation
confusion
tremor, shivering, muscle jerking
sweating
headache
tachycardia
hypertonia/rigidity
diaphoresis
flushing
dilated pupils
hyperthermia
myoclonus
startling

Full details

Risk factors

exposure to a serotonergic drug
exposure to two or more serotonergic drugs

Full details

Diagnostic tests

1st tests to order

clinical diagnosis

Full details

Tests to consider

CBC
creatine phosphokinase
ECG
blood cultures
lumbar puncture
CT or MRI head

Full details

Treatment algorithm

ACUTE

severe serotonin toxicity

moderate serotonin toxicity

mild serotonin toxicity

Contributors

Authors

Geoffrey Isbister, BSc, MBBS, FACEM, MD

Clinical Toxicologist

Calvary Mater Newcastle

Associate Professor

University of Newcastle

Newcastle

Australia

Disclosures

GI is an author of several references cited in this monograph.

Peer reviewers

Laura Tormoehlen, MD, FAAN, FACMT

Neurologist and Medical Toxicologist

Associate Professor of Clinical Neurology and Emergency Medicine

Indiana University

Bloomington

Disclosures

LT has been compensated as an expert witness for cases involving serotonergic drugs.

Daniel E Brooks, MD

Medical Director, Banner Poison and Drug Information Center

Phoenix

Disclosures

DEB declares that he has no competing interests.

Karl Marlowe, MbChB, MSc, PgC-Ed, PgD-CBT, MRCPsych

Consultant Psychiatrist

East London NHS Foundation Trust

London

Disclosures

KM declares that he has no competing interests.

Theodore A. Stern, MD

Chief

Psychiatric Consultation Service

Massachusetts General Hospital

Professor of Psychiatry

Harvard Medical School

Boston

Disclosures

TAS declares that he has no competing interests.

Paul M. Gahlinger, MD

Adjunct Professor

Department of Family and Preventive Medicine

University of Utah

Salt Lake City

Disclosures

PMG declares that he has no competing interests.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

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

Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626 Abstract

Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28:205-214. Abstract

Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96:635-642.Full text Abstract

Chiew AL, Buckley NA. The serotonin toxidrome: shortfalls of current diagnostic criteria for related syndromes. Clin Toxicol (Phila). 2022 Feb;60(2):143-58. Abstract

Reference articles

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

Differentials
- Neuroleptic malignant syndrome (NMS)
- Sympathomimetic toxicity
- Anticholinergic delirium
More Differentials
Patient information
Serotonin syndrome
More Patient information
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Serotonin syndrome

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

severe serotonin toxicity

moderate serotonin toxicity

mild serotonin toxicity

Contributors

Authors

Geoffrey Isbister, BSc, MBBS, FACEM, MD

Disclosures

Peer reviewers

Laura Tormoehlen, MD, FAAN, FACMT

Disclosures

Daniel E Brooks, MD

Disclosures

Karl Marlowe, MbChB, MSc, PgC-Ed, PgD-CBT, MRCPsych

Disclosures

Theodore A. Stern, MD

Disclosures

Paul M. Gahlinger, MD

Disclosures

Peer reviewer acknowledgements

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