A psychiatry resident is studying serotonin syndrome vs neuroleptic malignant syndrome (NMS). Which clinical finding most reliably distinguishes serotonin syndrome from NMS?

• A Neuromuscular hyperactivity (clonus, hyperreflexia, myoclonus, tremor) with rapid onset (hours) in serotonin syndrome vs. 'lead-pipe' rigidity with insidious onset (days) in NMS ✓
• B Fever and diaphoresis; both present equally in both conditions
• C Elevated CK is pathognomonic of serotonin syndrome only
• D Rhabdomyolysis occurs exclusively in NMS

Explanation

Serotonin syndrome (caused by serotonergic excess) is characterised by the Hunter triad: (1) neuromuscular hyperactivity — clonus (especially inducible and ocular), hyperreflexia, myoclonus, tremor; (2) autonomic instability; (3) altered mental status. Onset is rapid (within hours of drug initiation or change). NMS (caused by dopamine D2 receptor blockade) features 'lead-pipe' muscular rigidity, hyporeflexia, and insidious onset over 1–3 days. Both can cause fever and elevated CK; however, the key distinguishing feature is the neuromuscular activity type — hyperreflexia/clonus in serotonin syndrome vs. rigidity/hyporeflexia in NMS. Treatment: serotonin syndrome — cyproheptadine (5-HT2A antagonist); NMS — dopamine agonists (bromocriptine), dantrolene.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

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