Which antidepressant is contraindicated in a patient taking tramadol for chronic pain, due to risk of serotonin syndrome, while also being an inhibitor of CYP2D6?
- A Mirtazapine
- B Agomelatine
- C Vortioxetine
- D Fluoxetine ✓
Explanation
Fluoxetine is both a serotonin reuptake inhibitor (increasing synaptic serotonin) and a potent CYP2D6 inhibitor. Tramadol is metabolized by CYP2D6 to its active O-desmethyltramadol (M1 metabolite), which is the main opioid-active component. CYP2D6 inhibition by fluoxetine reduces tramadol's opioid analgesic effect but, crucially, fluoxetine's serotonin activity combined with tramadol's serotonin reuptake inhibition markedly raises serotonin syndrome risk. Mirtazapine (NaSSA) and agomelatine (melatonin agonist) have minimal serotonin syndrome potential; vortioxetine is a serotonin modulator and has some risk but is not a CYP2D6 inhibitor.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.