Miley Nguyen, PharmD & Husna Rahim, PharmD
Mental Health in Pregnancy: Advancing Care Through Pharmacogenomics. How can pharmacogenomics (PGx) enhance mental health treatment during pregnancy? Hormonal fluctuations during pregnancy significantly increase the risk of mood disorders in expecting mothers, with 10% of pregnant women globally experiencing mental health episodes (World Health Organization). Inadequate treatment in pregnancy can contribute to poor maternal outcomes, including preterm birth and low infant birth weight. Baseline PGx testing helps optimize psychiatric treatments before conception, while continued testing during pregnancy accommodates physiological changes that impact drug response, ensuring sustained mental health stability for both mother and child.
During pregnancy, activity in CYP2D6 fluctuates and CYP2C19 decreases. Pregnancy introduces physiological changes that affect how psychiatric medications behave in the body. Hormonal fluctuation and altered organ function impact drug metabolism and response. Many psychiatric medications, including antidepressants and antipsychotics, rely on enzymatic pathways that exhibit genetic variability, most notably CYP2D6 and CYP2C19. Changes in enzyme activity can affect therapeutic outcomes of psychiatric treatments. Clinical studies have shown that during pregnancy, CYP2D6 activity fluctuates and CYP2C19 activity decreases, which makes predicting responses to therapy especially challenging (Betcher & George, 2020).
Poor metabolizers are at risk of drug toxicity. CYP2C19 poor metabolizers may experience elevated levels of medications like citalopram, increasing the risk of toxicity, including serotonin syndrome or heightened sedation (Betcher & George, 2020). Similarly, CYP2D6 ultra-rapid metabolizers (UM) break down drugs like paroxetine too quickly, leading to subtherapeutic blood levels and potentially inducing withdrawal symptoms, worsening depression, and psychiatric episodes. This is corroborated by CPIC guidelines, which do not recommend paroxetine for UMs due to the risk of insufficient drug exposure (Ververs et al., 2009; CPIC, n.d.).
All medication carry risk of congenital abnormalities. PGx testing at baseline allows for proactive medication management, improving mental health stability before conception and minimizing the need for major medication adjustments during pregnancy. It should be noted that PGx testing does not predict which psychotropic medications are safe to use during pregnancy, as all medications carry some risk of congenital abnormalities regardless of metabolism status. Expanding research into PGx in pregnancy will continue to optimize perinatal psychiatric care, improving both maternal and neonatal health outcomes (Betcher & George, 2020).
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