A 28-year-old man is brought to the emergency with agitation, tachycardia (HR 130/min), hypertension, hyperthermia, diaphoresis, dilated pupils, and hyperreflexia with lower limb clonus after using multiple recreational drugs. Which diagnosis and antidote combination is correct?

• A NMS; dantrolene + bromocriptine
• B Serotonin syndrome; cyproheptadine + benzodiazepines ✓
• C Anticholinergic toxidrome; physostigmine
• D Sympathomimetic toxidrome; beta-blockers as first line

Explanation

Clonus (particularly inducible ocular and lower limb clonus) is the pathognomonic feature distinguishing Serotonin Syndrome from NMS and other hyperadrenergic states. The Hunter Criteria for serotonin toxicity require clonus (spontaneous, inducible, or ocular) plus one of: agitation, diaphoresis, tremor, or hyperreflexia. Treatment includes cyproheptadine (5-HT2A antagonist, 12 mg loading then 2 mg q2h) and benzodiazepines for agitation. Anticholinergic syndrome lacks hyperreflexia/clonus and has absent bowel sounds. Pure beta-blockers are inappropriate as serotonin syndrome is not pure sympathomimetic toxicity.

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

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