Pharmacogenomic Characterization of Childbearing-Aged Individuals With Mood Disorders in a Tertiary Care Perinatal Mental Health Clinic

Jessica L. W. Mayer, MD ; Hannah K. Betcher, MD ; Laura J. Rasmussen-Torvik, PhD, MPH ; Amy Yang, MS ; Alfred L. George Jr, MD ; Tatiana Abramova, MS ; Catherine S. Stika, MD ; Katherine L. Wisner, MD, MS ; Crystal T. Clark, MD, MSc ; Jacqueline Gollan, PhD

J Clin Psychiatry. 2024;85(2):23m15024

Abstract

Objective: The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes. We determined the distribution of common pharmacogenetic variants, metabolizer phenotypes, past medication responses, and side effects in childbearing-aged individuals seeking treatment in a tertiary care perinatal mental health clinic.

Methods: Sixty treatment-seeking women (based on sex at birth) with DSM-5– defined bipolar disorder (n = 28) or major depressive disorder (n = 32) provided DNA samples and completed psychiatric diagnostic and severity assessments between April 2014 and December 2017. Samples were genotyped for single-nucleotide variants in drug metabolizing enzyme genes of commonly prescribed antidepressants (cytochrome P450 [CYP] 1A2, 2B6, 2C9, 2C19, 2D6, 3A4, and 3A5), and the frequency of normative metabolizer status was compared to reference populations data from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The Antidepressant Treatment History Form was used to record historic medication trials and side effects.

Results: A significantly greater proportion of extensive metabolizers for CYP2B6 was observed in the study population when compared to CPIC population frequency databases in Caucasians (0.64 vs 0.43 [95% CI: 0.49–0.76]; P value = .006) and African Americans (0.71 vs 0.33 [95% CI: 0.29–0.96]; P value = .045). No significant association was found between metabolizer phenotype and the likelihood of a medication side effect.

Conclusion: Pharmacogenomic testing may have value for personalized prescribing in individuals capable of or considering pregnancy.

J Clin Psychiatry 2024;85(2):23m15024

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