A patient on an SSRI for depression is started on tramadol for pain. Within 2 hours she develops agitation, diaphoresis, hyperthermia, and clonus. The most likely diagnosis and the primary receptor mechanism driving this syndrome is:
- A Serotonin syndrome — excessive 5-HT1A and 5-HT2A receptor stimulation ✓
- B Neuroleptic malignant syndrome — dopamine D2 blockade
- C Anticholinergic toxidrome — muscarinic receptor blockade
- D Sympathomimetic toxidrome — excessive norepinephrine release
Correct answer: A. Serotonin syndrome — excessive 5-HT1A and 5-HT2A receptor stimulation
Explanation
Tramadol both inhibits serotonin reuptake and is a weak mu-opioid agonist. Combined with an SSRI, it precipitates serotonin syndrome by flooding serotonin receptors — particularly 5-HT1A (responsible for autonomic instability) and 5-HT2A (responsible for clonus and neuromuscular hyperactivity). The triad of mental status change, autonomic instability, and neuromuscular abnormalities (especially clonus) distinguishes serotonin syndrome from NMS, which develops gradually over days and lacks clonus.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.