Changes in antidepressant metabolism and dosing across pregnancy and early postpartum.
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.


METHODS
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 post-partum. 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-desmethylsertra-line 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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00279370.
Sit
Dorothy K
DK
Western Psychiatric Institute and Clinic, School of Medicine, University of Pittsburgh, PA 15213, USA. Sitdk@upmc.edu
Perel
James M
JM
Helsel
Joseph C
JC
Wisner
Katherine L
KL
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000627:therapeutic use*; D015283:Citalopram / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D019052:Depression, Postpartum / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications; D011296:Prenatal Diagnosis; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000627:therapeutic use*; D020280:Sertraline / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline