What are the clinical presentations of Serotonin (5-hydroxytryptamine) syndrome?

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From the Guidelines

Serotonin syndrome presents as a potentially life-threatening condition characterized by a triad of cognitive-behavioral changes, autonomic instability, and neuromuscular abnormalities, with the clinical presentation being extremely variable, making diagnosis challenging 1. The clinical triad of serotonin syndrome consists of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities.

  • Mental status changes may include agitation, restlessness, anxiety, disorientation, and tremor.
  • Autonomic hyperactivity may manifest as hyperthermia, tachycardia, hypertension, dilated pupils, flushing, diaphoresis, diarrhea, and hyperactive bowel sounds.
  • Neuromuscular abnormalities may include hyperreflexia, clonus, muscle rigidity, and myoclonus. According to the modified Dunkley criteria, the diagnosis can be made if the patient has taken a serotonergic drug within the last 5 weeks and has any of the following: tremor and hyperreflexia; spontaneous clonus; muscle rigidity, temperature >38°C, and either ocular clonus or inducible clonus; ocular clonus and either agitation or diaphoresis; or inducible clonus and either agitation or diaphoresis 1. Severe cases can lead to seizures, metabolic acidosis, rhabdomyolysis, renal failure, and death, with a mortality rate of approximately 11% 1. Management involves immediate discontinuation of all serotonergic agents, supportive care, and in moderate to severe cases, administration of serotonin antagonists such as cyproheptadine (initial dose 12mg orally, followed by 2mg every 2 hours until symptoms improve, then 8mg every 6 hours) 1.

From the Research

Presentation of Serotonin Syndrome

Serotonin syndrome presents with a range of clinical manifestations, including:

  • Alteration of mental status
  • Abnormalities of neuromuscular tone
  • Autonomic hyperactivity 2, 3, 4, 5, 6 These symptoms can occur alone or in combination, and may range in severity from mild to life-threatening.

Clinical Features

The clinical features of serotonin syndrome can be diverse and nonspecific, making diagnosis challenging 2, 4. Common clinical features include:

  • Neuromuscular excitation
  • Autonomic dysfunction
  • Altered mental status 3, 4, 5 These features can occur in patients undergoing new or altered serotonergic therapy.

Severity of Serotonin Syndrome

Serotonin syndrome can range in severity from mild to life-threatening 2, 3, 4. Most cases are mild and resolve with prompt recognition and supportive care, while more severe cases require inpatient hospitalization and aggressive management.

Drug-Induced Serotonin Syndrome

Serotonin syndrome can be induced by a variety of drugs, including:

  • Serotonergic agents alone or in combination with monoamine oxidase inhibitors 2, 3, 6
  • Intentional overdose of serotonergic drugs
  • Complex drug interactions between two or more serotonergic drugs 3, 6 Proper education and awareness about serotonin syndrome can improve diagnosis and promote appropriate treatment.

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

Serotonin syndrome-A focused review.

Basic & clinical pharmacology & toxicology, 2023

Research

Too much of a good thing? Diagnosis and management of patients with serotonin syndrome.

Emergency nurse : the journal of the RCN Accident and Emergency Nursing Association, 2022

Research

Serotonin syndrome.

Ochsner journal, 2013

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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