A 32-year-old man on tramadol for back pain is started on sertraline for depression. Two days later he develops agitation, tremor, diaphoresis, and temperature of 39°C. Ankle clonus is present. What is the mechanism of this reaction?
- A Excess serotonergic activity at 5-HT1A and 5-HT2A receptors ✓
- B Dopamine receptor blockade
- C Anticholinergic toxidrome
- D GABA-A receptor downregulation
Correct answer: A. Excess serotonergic activity at 5-HT1A and 5-HT2A receptors
Explanation
Tramadol inhibits serotonin and norepinephrine reuptake (in addition to weak opioid agonism). Combined with sertraline (SSRI), excess serotonergic stimulation at 5-HT1A (autonomic instability, hyperthermia) and 5-HT2A receptors (clonus, hyperreflexia, myoclonus) produces serotonin syndrome. The Hunter Criteria require one of: clonus (spontaneous, inducible, or ocular) in the context of a serotonergic agent. Treatment is cyproheptadine (5-HT2A antagonist) and supportive care; severe cases need ICU admission.
Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.
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