What is serotonin syndrome?

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From the Guidelines

Serotonin syndrome is a life-threatening medical condition caused by an excess of serotonin in the body, typically resulting from medication interactions, and requires immediate discontinuation of serotonergic medications and emergency medical attention. The condition is characterized by a triad of symptoms: mental status changes, autonomic instability, and neuromuscular abnormalities, as described in the study published in Pediatrics 1. Common causative agents include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), triptans, and certain antibiotics like linezolid.

Key Symptoms and Treatment

  • Mental status changes: agitation, confusion
  • Autonomic instability: hyperthermia, tachycardia, diaphoresis
  • Neuromuscular abnormalities: tremor, hyperreflexia, clonus
  • Treatment involves medication discontinuation, supportive care, and in severe cases, administration of serotonin antagonists like cyproheptadine, as recommended in the study 1
  • Benzodiazepines may be used for agitation and muscle rigidity, as mentioned in the study 1

Prevention and Management

Prevention is crucial through careful medication reconciliation and avoiding combinations of serotonergic drugs. The study 1 highlights the importance of recognizing the clinical diagnostic criteria for serotonin syndrome, with the Hunter criteria being most commonly used. Discontinuing the precipitating agent and providing supportive care, including treatment of agitation and management of autonomic instability, are essential steps in managing serotonin syndrome, as emphasized in the study 1. In severe cases, emergency sedation, neuromuscular paralysis, and intubation may be considered, as noted in the study 1.

From the Research

Definition and Causes of Serotonin Syndrome

  • Serotonin syndrome (SS) is a rare and potentially life-threatening toxic state caused by an adverse drug reaction that leads to excessive central and peripheral serotonergic activity 2.
  • It is characterized by a dose-relevant spectrum of clinical findings related to the level of free serotonin (5-hydroxytryptamine [5-HT]), or 5-HT receptor activation (predominantly the 5-HT1A and 5-HT2A subtypes) 3.
  • SS can occur after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors, and can range in severity from mild to life-threatening 2.

Clinical Features of Serotonin Syndrome

  • The clinical features of SS include alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity 2.
  • Common clinical features of SS include hyperreflexia, clonus, tachycardia, tremor, rigidity, increased bowel sound, diaphoresis, fever, hypertension, and myoclonus 4.
  • Neuromuscular excitation, such as tremor, hyperreflexia, and clonus, is a key feature of SS, along with autonomic dysfunction and altered mental status 5.

Diagnosis and Management of Serotonin Syndrome

  • The diagnosis of SS is based on clinical signs and symptoms, and can be confirmed by the presence of inducible clonus and agitation 6.
  • Management of SS involves withdrawal of the offending agent(s), aggressive supportive care to treat hyperthermia and autonomic dysfunction, and occasionally the administration of serotonin antagonists, such as cyproheptadine or chlorpromazine 2.
  • Supportive care, including intravenous fluids and intravenous lorazepam, can be effective in managing SS, and patients with moderate and severe cases of SS require inpatient hospitalization 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Overview of serotonin syndrome.

Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 2012

Research

Cyproheptadine in serotonin syndrome: A retrospective study.

Journal of family medicine and primary care, 2024

Research

High risk and low prevalence diseases: Serotonin syndrome.

The American journal of emergency medicine, 2022

Research

The serotonin syndrome-the need for physician's awareness.

International journal of emergency medicine, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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