Overview
Clinical Meaning
Serotonin syndrome is caused by excess serotonergic activity at central and peripheral 5 HT1A and 5 HT2A receptors.
WHNP
WHNP
Serotonin syndrome is caused by excess serotonergic activity at central and peripheral 5-HT1A and 5-HT2A receptors. It results from drug interactions increasing serotonin: increased synthesis (L-tryptophan), increased release (amphetamines, MDMA), decreased reuptake (SSRIs, SNRIs, TCAs, tramadol, dextromethorphan, St. John's Wort), decreased metabolism (MAOIs — most dangerous), or direct agonism (triptans, buspirone, fentanyl). The most dangerous combination is MAOI + SSRI/SNRI. The classic triad: (1) Altered mental status (agitation, confusion), (2) Autonomic instability (hyperthermia, tachycardia, diaphoresis, hypertension, mydriasis, diarrhea), (3) Neuromuscular hyperactivity (clonus — hallmark finding, hyperreflexia, myoclonus, tremor). The Hunter Criteria require a serotonergic agent plus: spontaneous clonus, inducible clonus + agitation/diaphoresis, ocular clonus + agitation/diaphoresis, tremor + hyperreflexia, or hypertonia + temperature >38°C + clonus. CLONUS distinguishes serotonin syndrome from NMS (which has lead-pipe rigidity and bradykinesia, NOT clonus).
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