A 25-year-old woman on fluoxetine for depression is also started on tramadol for post-operative pain. She develops agitation, clonus, hyperthermia, and diaphoresis. The most likely diagnosis and mechanism is:
- A NMS due to dopamine receptor blockade by tramadol
- B Serotonin syndrome due to excess synaptic serotonin from combined SSRI and tramadol's serotonin-releasing/reuptake-inhibiting properties ✓
- C Anticholinergic toxidrome from fluoxetine's muscarinic blocking effect
- D Opioid toxicity with paradoxical excitation
Correct answer: B. Serotonin syndrome due to excess synaptic serotonin from combined SSRI and tramadol's serotonin-releasing/reuptake-inhibiting properties
Explanation
Serotonin syndrome results from excess serotonergic neurotransmission and classically presents with the triad of altered mental status, autonomic dysfunction, and neuromuscular abnormalities (clonus is highly characteristic). Tramadol inhibits serotonin and norepinephrine reuptake in addition to its weak opioid agonism; combining it with an SSRI like fluoxetine creates dangerous serotonin excess. Treatment is drug withdrawal, cyproheptadine (5-HT2A antagonist), and supportive care.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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