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 care. 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, certain opioids, and some over-the-counter medications containing dextromethorphan.

Key Symptoms and Treatment

  • Mental status changes: agitation, confusion
  • Autonomic instability: hyperthermia, tachycardia, diaphoresis
  • Neuromuscular abnormalities: hyperreflexia, tremor, clonus Treatment involves:
  • Discontinuing the offending agents
  • Supportive care including IV fluids and temperature control
  • In severe cases, benzodiazepines for agitation and cyproheptadine (a serotonin antagonist) at a dose of 12mg initially followed by 2mg every 2 hours until symptoms improve, as recommended in the study 1.

Prevention and Management

Prevention is crucial through careful medication reconciliation, avoiding combinations of serotonergic drugs, and educating patients about potential interactions, including with herbal supplements like St. John's wort which can also increase serotonin levels. The mortality rate for serotonin syndrome is approximately 11%, with significant morbidity and mortality associated with the condition, highlighting the importance of prompt recognition and treatment 1.

From the Research

Definition and Causes of Serotonin Syndrome

  • Serotonin syndrome (SS) is a potentially life-threatening condition caused by excess stimulation of central nervous 5-hydroxytryptamine (5HT)-1a and 5HT-2 receptors 2
  • It is an iatrogenic condition caused by serotonergic agents, often resulting from the simultaneous use of two or more serotonergic drugs 3, 4
  • The syndrome can also occur after the initiation of a single serotonergic drug in a susceptible individual, the addition of a second or third agent to long-standing doses of a maintenance serotonergic drug, or after an overdose 4

Clinical Features of Serotonin Syndrome

  • The clinical features of SS include alterations in mental status, autonomic instability, and neuromuscular abnormalities such as tremor, hyperreflexia, or myoclonus 2
  • Common clinical features of SS include hyperreflexia, clonus, tachycardia, tremor, rigidity, increased bowel sound, diaphoresis, fever, hypertension, and myoclonus 3
  • The diagnosis of SS requires a history of exposure to agents active at serotonin receptors and the presence of these clinical features 2

Diagnosis and Treatment of Serotonin Syndrome

  • The diagnosis of SS is mainly clinical, and diagnostic criteria may miss out on some cases 5
  • The treatment of SS involves the administration of a serotonin antagonist, such as cyproheptadine, and supportive care 3, 2
  • The role of specific serotonin receptor antagonists, such as cyproheptadine, in the treatment of SS remains to be delineated, and its use should be considered an adjunct to supportive care 2
  • In mild to moderate cases, SS typically resolves within the first 24 hours after initiating therapy and discontinuation of the serotoninergic medications 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treatment of the serotonin syndrome with cyproheptadine.

The Journal of emergency medicine, 1998

Research

Cyproheptadine in serotonin syndrome: A retrospective study.

Journal of family medicine and primary care, 2024

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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