Serotonin Syndrome (Drug-Induced)



  • Constellation of signs and symptoms from excessive serotonin and stimulation of central and peripheral serotonergic receptors
  • Spectrum of symptoms may range from mild and subtle findings to severe and sometimes fatal toxicity
  • Results from use of serotonergic agents, alone or in combination with other serotonergic agents (may be therapeutic, intentional overdose, recreational, drug interactions)
  • Classic triad:
    • Autonomic dysfunction: Hyperthermia, diaphoresis, tachycardia, and hypertension
    • Cognitive changes: Confusion, agitation, hallucinations, decreased responsiveness
    • Neuromuscular excitability: Hyperreflexia, myoclonus, tremors


Incidence and Prevalence Estimates
  • SSRIs implicated most often, alone or in combination with other drugs
  • Incidence higher in females but fatalities greater in males
  • Highest incidence in ages 19–39
  • Most fatalities from drug/drug interactions or recreational abuse


  • Serotonin produced by metabolism of L-tryptophan
  • Exerts action on 5-hydroxytryptophan (5-HT) receptors of which there are 7 types located in central and peripheral nervous systems:
    • Influences sleep and temperature regulation, affective behavior, food intake, migraines, emesis, sexual behavior, nociception, motor tone, GI motility, and vascular tone
  • Extensive list of serotonergic agents, with psychiatric meds most common (SSRIs, SNRIs):
    • Examples: Citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, trazodone, venlafaxine
  • Other serotonergic agents include (not exhaustive):
    • Buspirone, cocaine, dextromethorphan, fentanyl, lithium, MAOIs, MDMA (ecstasy), meperidine, methadone, metoclopramide, ondansetron, selegiline, St. John wort, TCAs, tramadol, triptans (controversial)

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