Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study
Farhana Islam, Leen Magarbeh, Samar S. M. Elsheikh, Stefan M. Kloiber, Caroline Wanderley Espinola, Venkat Bhat, Benicio Noronha Frey, Roumen V. Milev, Claudio N. Soares, Sagar V. Parikh, et al.
The Canadian Journal of Psychiatry2023 (epub Oct 2023)
Summary (paraphrased)
In 178 adults with major depressive disorder treated with escitalopram (weeks 0-8), nonresponders were augmented with aripiprazole while responders continued escitalopram alone (weeks 8-16), with sexual function and satisfaction tracked on the SexFX scale. CYP2C19 intermediate and poor metabolizers showed treatment-related improvement in sexual arousal during weeks 8-16, whereas normal metabolizers showed a decline (F(2,54) = 8.00, p < 0.001, q = 0.048). No significant associations were found for CYP2D6 or ABCB1 variants, and the CYP2C19 effect ran opposite to the authors' initial hypothesis, which they attribute partly to serum drug and metabolite (S-DCT) exposure patterns. The authors note this is the first study of treatment-emergent sexual dysfunction genetics under escitalopram with aripiprazole augmentation, and that findings need replication in a larger independent sample.
Why it’s in the systems review
This is the most directly on-point susceptibility-marker study for the PSSD axis yet found outside the corpus: it links measured CYP2C19 metabolizer status to on-treatment changes in sexual arousal, with serum drug levels as an exposure bridge. It complements the corpus's CYP2D6-focused Discord records by adding CYP2C19 and the blood-brain-barrier transporter ABCB1 to the candidate susceptibility panel, and its unexpected direction of effect is a cautionary data point for any treatment-candidate search that would stratify patients by metabolizer status.
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