A patient with treatment-resistant depression fails multiple SSRIs and SNRIs. Pharmacogenomic testing reveals ultrarapid CYP2C19 metabolizer status. This genotype most directly explains poor response to which antidepressant?
- A Venlafaxine
- B Mirtazapine
- C Escitalopram ✓
- D Bupropion
Explanation
Escitalopram and citalopram are primarily metabolised by CYP2C19 (and CYP3A4 secondarily). In CYP2C19 ultrarapid metabolizers (~5% of Asians, 3% of Caucasians), escitalopram is eliminated so rapidly that therapeutic plasma concentrations are not maintained at standard doses, explaining treatment failure. Venlafaxine is mainly metabolised by CYP2D6 to its active metabolite O-desmethylvenlafaxine. Mirtazapine uses CYP1A2, 2D6, and 3A4. Bupropion is metabolised by CYP2B6. CYP2C19 ultrarapid status is the most clinically actionable pharmacogenomic finding for escitalopram dosing.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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