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Changes in Antidepressant Metabolism and Dosing Across Pregnancy and Early Postpartum
Dorothy K. Sit, M.D.; James M. Perel, Ph.D.; Joseph C. Helsel, B.S.; and Katherine L. Wisner, M.D., M.S.
Objective: Little information about the disposition of individual antidepressant drugs during pregnancy has been published. We examined the dose requirements and level-to-dose (L/D) ratios of citalopram, escitalopram, and sertraline during pregnancy and after birth.
Method: Women aged from 32 to 43 years with major depressive disorder according to the Structured Clinical Interview for DSM-IV Axis I Disorders participated in the study. Doses were charted across each week of gestation and postpartum. Samples were collected at 20, 30, and 36 weeks' gestation; delivery; and at 2 and 12 weeks postpartum. Plasma trough levels were obtained 8 to 15 hours after dose intake. Across pregnancy and postpartum, the mean dose-corrected plasma concentrations (L/D ratios) of S- and R-citalopram and S-sertraline, and the corresponding primary chiral metabolites S- and R-desmethylcitalopram and N-desmethylsertraline were assessed. The samples were analyzed for concentrations of stereospecific parent drug and metabolites. The study was conducted from 2003 to 2006.
Results: Three women received citalopram, 2 women were treated with escitalopram, and 6 women received sertraline. In 4 of 5 subjects who received citalopram or escitalopram and 5 of 6 subjects who received sertraline, the L/D ratios for the stereoisomers of the parent compound and primary metabolite decreased between 20 weeks gestation and delivery, which reflects increased drug metabolism. By 12 weeks postpartum the L/D ratios were similar to those detected at 20 weeks gestation.
Conclusions: Our cases illustrate that dose requirements frequently increase during the second half of pregnancy to offset increased drug turnover and maintain optimal pharmacotherapy. These findings replicate and extend earlier published data with other antidepressants.
Trial Registration: clinicaltrials.gov Identifier: NCT00279370
(J Clin Psychiatry 2008;69:652-658. Online Ahead of Print March 11, 2008.)
Received May 1, 2007; accepted October 15, 2007. From the Western Psychiatric Institute and Clinic, School of Medicine, University of Pittsburgh, Pa.
Funding for this article was provided by National Institute of Mental Health grant R01 MH60335 for the study Antidepressant Drug Use in Pregnancy and by Junior Faculty Scholars R25 Program 5 R25 MH060473-08.
Dr. Wisner has received research/grant support from the National Institute of Mental Health, Stanley Medical Research Foundation, New York-Mid-Atlantic Consortium for Genetics and Newborn Screening Services, State of Pennsylvania, American Society for Bariatric Surgery, Pfizer, and Wyeth and serves on the speakers bureau of GlaxoSmithKline. Drs. Sit and Perel and Mr. Helsel report no additional financial or other relationships relevant to the subject of this article.
Corresponding author and reprints: Dorothy K. Sit, M.D., Western Psychiatric Institute and Clinic, University of Pittsburgh, 3811 O'Hara St., Oxford 410, Pittsburgh, PA 15213 (e-mail: Sitdk@upmc.edu).