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Serotonin Syndrome

Homepage: EMNote.org ■ 🚩Membership: https://tinyurl.com/joinemnote 🚩ACLS Lecture: https://tinyurl.com/emnoteacls Serotonin Syndrome Introduction to Serotonin Syndrome Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonin activity in the central nervous system. This presentation will cover the causes, clinical features, diagnosis, treatment, and prevention of serotonin syndrome. Pathophysiology of Serotonin Syndrome Serotonin (5-hydroxytryptamine) is a neurotransmitter involved in mood regulation, thermoregulation, and autonomic functions. Serotonin syndrome results from overstimulation of postsynaptic serotonin receptors, particularly 5-HT1A and 5-HT2A. Excessive serotonin disrupts cognitive, autonomic, and neuromuscular functions, leading to a triad of symptoms. Causes of Serotonin Syndrome Most commonly caused by serotonergic drugs that increase serotonin levels or enhance its activity. Key drug classes: Antidepressants (SSRIs, SNRIs, MAOIs, tricyclic antidepressants). Pain medications (Tramadol, Meperidine). Over-the-counter drugs (Dextromethorphan). Combining multiple serotonergic agents or overdosing significantly increases risk. Approximately 10% of cases occur after an overdose of serotonergic medications. Addition of drugs that inhibit CYP2D6 and CYP3A4 to SSRI regimens MAOIs combined with meperidine, dextromethorphan, SSRIs, or MDMA ("ecstasy") Clinical Features Symptoms typically appear within 2 to 24 hours after starting or increasing a serotonergic drug. Cognitive and Behavioral Symptoms: Agitation, restlessness, confusion, anxiety, disorientation, hallucinations. Autonomic Symptoms: Fever, tachycardia, hypertension, hyperthermia (above 41°C indicates poor prognosis), diaphoresis, diarrhea, dilated pupils. Neuromuscular Symptoms: Hyperreflexia, myoclonus (muscle twitching), tremors, muscle rigidity, incoordination, short-lived seizures. Spectrum of Manifestations Clinicians may dismiss symptoms as inconsequential or unrelated to drug therapy. Anxiety and akathisia may be misattributed to the patient's mental state. Lack of awareness about serotonin syndrome, despite its prevalence across all ages. Diagnosis of Serotonin Syndrome Diagnosis is clinical, based on history, symptom evaluation, and exclusion of other conditions. Key diagnostic steps: Recent use or dose change of serotonergic drugs. Identification of the triad of cognitive, autonomic, and neuromuscular symptoms. Rule out neuroleptic malignant syndrome, rhabdomyolysis, and other metabolic or psychiatric conditions. Myoclonus and lower extremity muscle rigidity are key distinguishing features. Treatment of Serotonin Syndrome Primary intervention: Discontinuation of serotonergic drugs (symptoms usually resolve within 24 hours, except for fluoxetine due to its long half-life). Supportive care: Intravenous fluids, oxygen therapy, antipyretics for fever. Pharmacological management: Benzodiazepines for agitation, seizures, and muscle rigidity. Cyproheptadine (serotonin antagonist) administered orally, though its efficacy is uncertain. Severe cases: May require mechanical ventilation and intensive care (25% of severe cases need intubation). Complications and Prevention Complications: Rhabdomyolysis, metabolic acidosis, long-term cognitive impairments in severe cases. Prevention: Careful medication review to avoid combining serotonergic agents. Use drug interaction databases to assess risks. Educate patients on the risks of serotonergic drugs and the importance of reporting new symptoms promptly. Prognosis of Serotonin Syndrome Most patients recover fully with timely recognition and treatment. Severe cases, especially those with hyperthermia or refractory seizures, have a higher risk of mortality. Long-term outcomes depend on the severity and duration of the syndrome.