Harvey's Garden

Serotonin syndrome

2 min read

Epidemiology

Etiology

Serotonergic drugs

  • Antidepressants (e.g., MAOIs, SSRIs, SNRIs, tricyclic antidepressants, vortioxetine, vilazodone, trazodone)
  • Anxiolytics (e.g., buspirone)
  • Anticonvulsants (e.g., valproate)
  • Opioids (e.g., tramadol, meperidine)
  • NMDA receptor antagonists (e.g., dextromethorphan)
  • 5-HT3 receptor antagonists (e.g., ondansetron)
  • Serotonin receptor agonists (e.g., triptans, ritonavir)
  • Antibiotics (e.g., linezolid) t
    • It possesses weak monoamine oxidase inhibitor (MAOI) activity. Co-administration of an MAOI (Linezolid) with a serotonergic agent (Paroxetine) prevents the breakdown of serotonin, leading to synaptic accumulation and toxicity.
  • Herbal supplements (e.g., St. John’s wort, ginseng, tryptophan)
  • Recreational stimulants (e.g., MDMA, cocaine)

Tip

Serotonin syndrome rarely occurs with a single serotonergic drug used at therapeutic doses. More commonly, it is due to the combined effects of several serotonergic medications, overdose, and/or a drug-drug interaction. E.g. a depressed patient also takes linezolid.

Pathophysiology

Clinical features

  • Rapid onset (usually within 24 hours of starting/increasing dose).
  • Classic Triad:
    1. Mental Status Changes: Anxiety, agitation, delirium, confusion, coma.
    2. Autonomic Instability: Hyperthermia, tachycardia, hypertension, diaphoresis, diarrhea, mydriasis.
    3. Neuromuscular Hyperactivity: Hyperreflexia (lower extremities > upper), myoclonus, ocular clonus, tremor.
  • Key distinction: Patients are reflexive and wet (diaphoretic), unlike anticholinergic toxicity (dry) or NMS (rigid).

Tip

Sympathetic overactivity (dominant features) + GI hypermotility (the “exception”)

Diagnostics

Treatment

  • Agitation and excessive muscle activity: Treat with benzodiazepines.
  • Hyperthermia: Initiate cooling measures, e.g., by reducing ambient temperature, applying cooling blankets or ice packs, administering cold IV fluids.
  • Autonomic instability
    • Give antihypertensive treatment.
    • Treat MAOI-induced hypotension or shock.
  • Moderate to severe and/or refractory cases
    • Consider treatment with 5-HT2A receptor antagonists: cyproheptadine

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