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

ABSTRACT: 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 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. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00279370.

SUBMITTER: Sit DK

PROVIDER: S-EPMC2408825 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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

Sit Dorothy K DK Perel James M JM Helsel Joseph C JC Wisner Katherine L KL

The Journal of clinical psychiatry 20080401 4

<h4>Objective</h4>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.<h4>Method</h4>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 ...[more]

PMID: 18426260

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Project description:Aims/hypothesisThis study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; ISOGTT), insulin response and disposition index (DI) from late pregnancy (34-37 weeks gestation, T1), to early postpartum (1-5 days, T2) and late postpartum (6-12 weeks, T3). A secondary aim was to correlate the longitudinal changes in maternal lipids, adipokines, cytokines and weight in relation to the changes in ISOGTT, insulin response and DI.MethodsISOGTT, insulin response and DI were calculated at the three time points (T1, T2 and T3) using the results of a 75 g OGTT. Adipokines, cytokines and lipids were measured prior to each OGTT. Linear mixed-effects models were used to compare changes across each time point. Changes in ISOGTT, insulin response and DI were correlated with changes in maternal adipokines, cytokines and lipids at each time point.ResultsA total of 27 women completed all assessments. Compared with T1, ISOGTT was 11.20 (95% CI 8.09, 14.31) units higher at 1-5 days postpartum (p < 0.001) and was 5.49 (95% CI 2.38, 8.60) units higher at 6-12 weeks postpartum (p < 0.001). Compared with T1, insulin response values were 699.6 (95% CI 957.5, 441.6) units lower at T2 (p < 0.001) and were 356.3 (95% CI 614.3, 98.3) units lower at T3 (p = 0.004). Compared with T1, the DI was 6434.1 (95% CI 2486.2, 10,381.0) units higher at T2 (p = 0.001) and was 4262.0 (95% CI 314.6, 8209.3) units higher at T3 (p = 0.03). There was a decrease in mean cholesterol, triacylglycerol, LDL-cholesterol and VLDL-cholesterol from T1 to T2 (all p < 0.001), and an increase in mean C-reactive protein, IL-6 and IL-8 from T1 to T2 (all p < 0.001). Mean leptin decreased from T1 to T2 (p = 0.001). There was no significant change in mean adiponectin (p = 0.99) or TNF-α (p = 0.81) from T1 to T2. The mean maternal BMI decreased from T1 to T2 (p = 0.001) and T3 (p < 0.001). There were no significant correlations between any measure of change in ISOGTT, insulin response and DI and change in maternal cytokines, adipokines, lipids or weight from T1 to T2.Conclusions/interpretationIn women with GDM, delivery was associated with improvement in both insulin sensitivity and insulin production within the first few days. Improvement in insulin production persisted for 6-12 weeks, but insulin sensitivity deteriorated slightly. These changes in glucose metabolism were not associated to changes in lipids, leptin, inflammation markers or body weight.Trial registrationClinicalTrials.gov NCT02082301.

Project description:OBJECTIVES:This pilot study aimed to 1) follow the longitudinal changes in the salivary oxytocin level of pregnant women from late pregnancy to early postpartum, 2) examine the factors related to these changes, and 3) clarify the association of these changes with mother-infant bonding. METHODS:This study used a longitudinal observational design and questionnaires to obtain objective and subjective data. For oxytocin evaluation, saliva samples were collected and their oxytocin levels were measured at 4-time points [i.e., 1) 36-37 gestation weeks, 2) 38-39 gestation weeks, 3) 1-2 days postpartum, 4) 4-5 days postpartum]. The oxytocin level was assayed in duplicates by enzyme-linked immunosorbent assay. Baseline data were evaluated using the Parental Bonding Instrument (25 items), State Trait Anxiety Inventory (20 items), and Center for Epidemiologic Studies Depression Scale. Postpartum data were evaluated using the Mother to Infant Bonding Scale Japanese Version (10 items), Maternity Blues Scale (13 items), and 'Fatigue after Childbirth' using the Visual Analogue Scale (VAS: 0-100 mm). RESULTS:The participants were 13 primiparas with a mean age of 33 years. They had no depression or anxiety at the baseline. Their mean salivary oxytocin levels significantly increased from late pregnancy (36-39 gestation weeks) up to 1 day postpartum and then decreased until 5 days postpartum. There was a negligible correlation between the bonding disorder and the salivary oxytocin level on the 5th day after childbirth. A moderate correlation was observed between the maternity blues score and the salivary oxytocin level. There was a significant negative correlation between the postpartum fatigue and the salivary oxytocin level 1 day and 5 days after childbirth. CONCLUSION:The mean salivary oxytocin levels significantly increased from the baseline up to 1 day postpartum and then decreased until 5 days postpartum. The salivary oxytocin level was moderately associated with maternity blues and significantly with postpartum fatigue.

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

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

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