TY - JOUR
T1 - Changes in antidepressant metabolism and dosing across pregnancy and early postpartum
AU - Sit, Dorothy K.
AU - Perel, James M.
AU - Helsel, Joseph C.
AU - Wisner, Katherine L.
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
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U2 - 10.4088/JCP.v69n0419
DO - 10.4088/JCP.v69n0419
M3 - Article
C2 - 18426260
AN - SCOPUS:44849088194
SN - 0160-6689
VL - 69
SP - 652
EP - 658
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 4
ER -