A depressed patient on the SSRI fluoxetine for 4 weeks is started on tramadol for post-operative pain. He develops agitation, tremor, hyperreflexia, hyperthermia, and diaphoresis. The most likely diagnosis is:

• A Serotonin Syndrome ✓
• B Neuroleptic Malignant Syndrome
• C Anticholinergic toxidrome
• D Malignant hyperthermia

Explanation

Serotonin Syndrome results from excess serotonergic activity, classically caused by combinations of serotonergic drugs. Tramadol inhibits serotonin reuptake and increases serotonin release in addition to its weak opioid agonism. Combined with fluoxetine (strong SSRI and CYP2D6 inhibitor, which also increases tramadol's serotonergic metabolite exposure), this creates excess synaptic 5-HT. The triad is: (1) neuromuscular abnormalities (hyperreflexia, clonus, tremor), (2) autonomic instability (diaphoresis, tachycardia, hyperthermia), and (3) altered mental status. Onset is rapid (hours). NMS develops more slowly, involves rigidity and bradykinesia, and is associated with antipsychotics. Treatment: discontinue all serotonergic agents; cyproheptadine (5-HT2A antagonist) for mild-moderate cases.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.