Serotonin Syndrome

Serotonin Syndrome is a topic covered in the Washington Manual of Medical Therapeutics.

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General Principles

  • Serotonin syndrome is a clinical condition of neuromuscular abnormalities, mental status changes, and hyperthermia in patients exposed to serotonergic xenobiotics.
  • Serotonin syndrome is a spectrum of disease that ranges from mild to life-threatening.1
    • Some authors prefer the term “serotonin toxicity” or “serotonin excess” for all but the sickest patients.
    • Mild serotonin excess may not require any treatment or medical evaluation.
  • Serotonin syndrome classically develops when two or more serotonergic xenobiotics are coadministered, but it may also occur following an acute overdose of one or more serotonergic xenobiotics, dose titration of serotonergic xenobiotics, and initiation of therapy with a single serotonergic xenobiotic.

Pathophysiology

  • Serotonin syndrome is thought to occur due to excessive stimulation of 5HT1 and 5HT2 receptors.
  • Many classes of xenobiotics have been implicated in the development of the serotonin syndrome.
    • Psychotropics: SSRIs, TCAs, serotonin–norepinephrine reuptake inhibitors (SNRIs), MAO inhibitors, other atypical serotonergic antidepressants, bupropion, lithium, amphetamines, certain atypical antipsychotics
    • Opioids: meperidine, tramadol, dextromethorphan, and possibly fentanyl
    • Other pharmaceuticals: linezolid, triptans, valproate, lamotrigine, bromocriptine, methylene blue
    • Recreational drugs: methamphetamine and other amphetamines, cocaine, serotonergic hallucinogens (MDMA, psilocybin, tryptamine derivatives)

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General Principles

  • Serotonin syndrome is a clinical condition of neuromuscular abnormalities, mental status changes, and hyperthermia in patients exposed to serotonergic xenobiotics.
  • Serotonin syndrome is a spectrum of disease that ranges from mild to life-threatening.1
    • Some authors prefer the term “serotonin toxicity” or “serotonin excess” for all but the sickest patients.
    • Mild serotonin excess may not require any treatment or medical evaluation.
  • Serotonin syndrome classically develops when two or more serotonergic xenobiotics are coadministered, but it may also occur following an acute overdose of one or more serotonergic xenobiotics, dose titration of serotonergic xenobiotics, and initiation of therapy with a single serotonergic xenobiotic.

Pathophysiology

  • Serotonin syndrome is thought to occur due to excessive stimulation of 5HT1 and 5HT2 receptors.
  • Many classes of xenobiotics have been implicated in the development of the serotonin syndrome.
    • Psychotropics: SSRIs, TCAs, serotonin–norepinephrine reuptake inhibitors (SNRIs), MAO inhibitors, other atypical serotonergic antidepressants, bupropion, lithium, amphetamines, certain atypical antipsychotics
    • Opioids: meperidine, tramadol, dextromethorphan, and possibly fentanyl
    • Other pharmaceuticals: linezolid, triptans, valproate, lamotrigine, bromocriptine, methylene blue
    • Recreational drugs: methamphetamine and other amphetamines, cocaine, serotonergic hallucinogens (MDMA, psilocybin, tryptamine derivatives)

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