Abstract
Rationale Few studies of the effect of the dynamic physiologic changes during pregnancy on plasma concentrations of fluoxetine (FLX) have been published. Objectives We determined the change in concentration to dose (C/D) ratios of R- and S-FLX and R- and S-norfluoxetine monthly during pregnancy and postpartum, assessed their relationships to cytochrome P450 (CYP) 2D6 and CYP2C9 metabolizer phenotypes, and evaluated the course of their depressive and anxiety symptoms. Methods In this observational study, 10 FLX-treated pregnant individuals provided blood samples at steady state every 4 weeks during pregnancy and once postpartum for measurement of plasma FLX and norfluoxetine enantiomer concentrations. Participants were genotyped for variants in CYP2C9 and CYP2D6 using commercial assays with Taqman probes. At each assessment, depressive and anxiety symptoms were quantified. Results The C/D ratios of all FLX and norfluoxetine enantiomers, and the active moiety, decreased steadily through pregnancy and rose after birth. In the final trimester, the mean C/D ratio of the active moiety was 24.9% lower compared with the mean nonpregnant, 12-week postpartum C/D ratio. One individual with CYP2D6 ultrarapid metabolizer status was prescribed the highest FLX dose among participants. In these treated individuals, the mean depressive and anxiety symptoms remained in the mild range across the perinatal period. Conclusions These data do not support a recommendation for routine plasma concentration monitoring or CYP2D6 pharmacogenetic testing for pregnant people treated with FLX; however, monitoring for symptom relapse is recommended because of declining plasma drug concentrations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 100-106 |
| Number of pages | 7 |
| Journal | Journal of clinical psychopharmacology |
| Volume | 44 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2024 |
Funding
This study, Optimizing Medication Management for Mothers with Depression (OPTIMOM, NICHD 1U54HD085601‐01, Clinical Trials.gov ID NCT02519790, PIs: KL Wisner, C Stika, A George), was supported by The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [U54HD047891, U54HD047905, and U54HD085601]. These data were obtained from the study Optimizing Medication Management for Mothers with Depression (OPTI-MOM, Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] 1U54HD085601, ClinicalTrials.gov ID NCT02519790, MPI: K.L.W., C.S.S., A. L.G.), which was supported by the NICHD (U54HD047891, U54HD047905, and U54HD085601) from the National Institutes of Health, the Obstetric-Fetal Pharmacology Research Center (OPRC), the Asher Center for the Study and Treatment of Depressive Disorders, the Center for Pharmacogenomics, and the Northwestern University Feinberg School of Medicine. The following authors declare no conflicts of interest: K.L.W., M.J.A., C.S.S., A.Y., T.V.A., S.N.C., and M.M.C. A.L.G. reports service on the advisory board and research funding from Tevard Biosciences, consulting, and receipt of research funding from Praxis Precision Medicines, and receipt of research funding from Neurocrine Biosciences. DATA AVAILABILITY STATEMENT The research reported in this publication was supported, in part, by the National Institutes of Health's (NIH's) National Center for Advancing Translational Sciences, grant UL1TR001422. This work was also supported by the Mary Beth Donnelley Clinical Pharmacology Core Facility at Northwestern University and NIH S10 OD021786.
Keywords
- R/S fluoxetine
- R/S norfluoxetine
- anxiety
- cytochrome P450 2D6
- depression
- pharmacogenetics
- postpartum
- pregnancy
- selective serotonin reuptake inhibitors
ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology (medical)
