Selective Serotonin Reuptake Inhibitor Pharmacokinetics During Pregnancy: Clinical and Research Implications

Ethan A Poweleit; Margaret A Cinibulk; Sarah A Novotny; Melissa Wagner-Schuman; Laura B Ramsey; Jeffrey R Strawn

doi:10.3389/fphar.2022.833217

Selective Serotonin Reuptake Inhibitor Pharmacokinetics During Pregnancy: Clinical and Research Implications

Front Pharmacol. 2022 Feb 25:13:833217. doi: 10.3389/fphar.2022.833217. eCollection 2022.

Authors

Ethan A Poweleit^{1

2

3

4}, Margaret A Cinibulk⁵, Sarah A Novotny⁶, Melissa Wagner-Schuman⁷, Laura B Ramsey^{3

4}, Jeffrey R Strawn^{3

7

8}

Affiliations

¹ Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
² Department of Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
³ Department of Pediatrics, Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
⁴ Department of Pediatrics, Division of Research in Patient Services, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
⁵ Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, United States.
⁶ Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Mississippi, Jackson, MS, United States.
⁷ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, United States.
⁸ Department of Pediatrics, Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Abstract

Pregnancy and associated physiologic changes affect the pharmacokinetics of many medications, including selective serotonin reuptake inhibitors-the first-line pharmacologic interventions for depressive and anxiety disorders. During pregnancy, SSRIs exhibit extensive pharmacokinetic variability that may influence their tolerability and efficacy. Specifically, compared to non-pregnant women, the activity of cytochrome P450 (CYP) enzymes that metabolize SSRIs drastically changes (e.g., decreased CYP2C19 activity and increased CYP2D6 activity). This perspective examines the impact of pharmacokinetic genes-related to CYP activity on SSRI pharmacokinetics during pregnancy. Through a simulation-based approach, plasma concentrations for SSRIs metabolized primarily by CYP2C19 (e.g., escitalopram) and CYP2D6 (e.g., fluoxetine) are examined and the implications for dosing and future research are discussed.

Keywords: SSRI (selective serotonergic reuptake inhibitors); anxiety; depression; pharmacokinctics; pregnancy.

Abstract

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