A patient on phenelzine (MAOI) for depression self-administers tramadol for back pain. Within 2 hours he develops agitation, diaphoresis, tremor, myoclonus, hyperreflexia, and clonus at the ankles. His temperature is 38.9°C. What is the most accurate differentiating feature from NMS?

• A Presence of fever
• B Ankle clonus and hyperreflexia (neuromuscular excitability) ✓
• C Autonomic instability
• D Elevated serum CK

Explanation

Serotonin syndrome is distinguished from NMS by the presence of neuromuscular excitability features — particularly clonus (especially inducible clonus at the ankles and knees) and hyperreflexia. NMS characteristically causes lead-pipe rigidity and decreased reflexes due to dopamine blockade. Both conditions share fever and autonomic instability. The Hunter Serotonin Toxicity Criteria specifically require clonus or hyperreflexia for diagnosis. Tramadol plus MAOIs is a classic precipitant of serotonin syndrome.

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

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