Navya Brinda & Jennifer Tovar, PharmD
Have YOU EVER WONDERED…how genetics shapes antidepressant response in women?
- Women face a higher risk of depression due to hormonal fluctuations and genetic polymorphisms in serotonin-related pathways (Radosavljevic et al., 2023).
- Sex-specific differences in drug metabolism, especially through CYP450 enzymes influence antidepressant efficacy, side effect risk, and treatment continuity
- Pharmacogenomic (PGx) testing empowers personalized antidepressant selection
The Challenge.
Women have a higher risk of depression, which is shaped by hormonal, genetic, and reproductive factors. Yet, treatment often overlooks key sex-specific differences and genetic variations.
- Women are significantly more likely than men to experience depression (Hodes & Epperson, 2019). Sex-specific polymorphisms in serotonin transporters, receptors, and the MAO-A enzyme contribute to increased susceptibility and variable treatment response in women (Radosavljevic et al., 2023).
- CYP2D6 and CYP3A4 are two of the most important enzymes involved in metabolizing widely used antidepressants. However, these enzyme activities have sex-specific factors (Radosavljevic et al., 2023). For example, CYP3A4 tends to be more active in younger women, leading to faster drug clearance and reduced blood concentrations (Schwartz, 2003).
- CYP2D6 activity can also change during pregnancy, leading to increased side effects such as weight gain, reduced antidepressant effectiveness, unresolved symptoms, and often resulting in early treatment discontinuation (Radosavljevic et al., 2023; Bérard et al., 2017)
Benefits & Real-World Applications of PGx.
Metabolic differences, particularly those influenced by sex and genetics, underscore the value of pharmacogenomics (PGx) in guiding safer, more effective, and personalized treatment decisions.
- For example, variations in CYP2D6 can influence how a woman metabolizes antidepressants. Reduced CYP2D6 activity may lead to slower drug breakdown and elevated plasma levels, increasing the risk of side effects, while ultrarapid metabolism may result in subtherapeutic exposure and diminished efficacy (Bérard et al., 2017). .
- In one illustrative case, PGx testing in a 27-year-old woman with persistent depressive symptoms revealed intermediate CYP2C19 metabolism, which reduced the clearance of her current medication, citalopram, and increased the risk of toxicity. Her treatment dosing was adjusted accordingly, leading to symptom improvement without serious side effects (Zhang Y. & Yue W., 2025).
Conclusion.
PGx helps bridge this gap by guiding treatment selection based on an individual’s genetic makeup.
- Pharmacogenomics offers a valuable path toward more precise and effective depression treatment in women by accounting for individual genetic, metabolic, and hormonal differences that impact how antidepressants, such as SSRIs, SNRIs, are processed and tolerated.
Learn more about UGenome.
Personalized Medication Service, ProPEx, or contact UGenome. You can also find case studies for UGenome’s bioinformatics services Metabolite Identification, Bone Metastasis Risk Analysis in Breast Cancer, Survival Analysis with gene signatures in cancer
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