Pharmacokinetics of clomipramine during pregnancy.

PURPOSE: Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pregnancy. Second, we describe Center for Epidemiologic Studies Depression scale (CES-D) scores during pregnancy. METHODS: During 13 pregnancies, every trimester and 3 months after pregnancy, the clomipramine and desmethylclomipramine concentrations were measured with LC-MSMS and the severity of depression was assessed by taking the CES-D score. All concentrations used in our calculations were in fact the ratio between actual plasma concentration (µg/l) and the actual dose (mg). We compared differences in ratios between trimesters by using the Friedman test. RESULTS: Studying 12 women and 13 pregnancies, we found no changes in mean clomipramine concentrations, a statistically significant decrease in mean desmethylclomipramine concentrations (p = 0.014) and a significant decrease in the ratio of desmethylclomipramine/clomipramine mean concentrations during pregnancy (p = 0.014) compared to the post-partum period. Sub-therapeutic concentrations of clomipramine and desmethylclomipramine were found in three patients during whole pregnancy. CONCLUSIONS: The mean concentrations of the pharmacologically active metabolite of clomipramine and desmethylclomipramine changes during pregnancy, where a decrease in mean concentrations was found during pregnancy. In case of recurrent disease, we recommend to control clomipramine and its metabolite concentrations, while both are active.

In utero exposure to antidepressants and the use of drugs for pulmonary diseases in children.

PURPOSE: The use of antidepressants during pregnancy is common. Some studies suggest an association between in utero exposure to antidepressants and the occurrence of pulmonary diseases like asthma later in life. Serotonin reuptake inhibitors (SSRIs) as well tricyclic antidepressants (TCAs) are thought to be involved in the development of the respiratory rhythm generator (RRG) and the maturation of the formation of surfactant. In this study the use of drugs for pulmonary diseases in children who were exposed to antidepressants in utero were compared with non-exposed children. METHODS: The pharmacy prescription database IADB.nl was used for a cohort study in which the use of drugs for pulmonary disease in children after in utero exposure to antidepressants (TCAs, SSRIs) was compared with children with no antidepressant exposure in utero. Drugs for pulmonary diseases were applied as a proxy for disturbed development of the respiratory tract. RESULTS: A small though significant increase in the incidence risk ratio (IRR) of the use of drugs for pulmonary disease was found after any-time in utero exposure to SSRIs, adjusted for maternal use of antibiotics, of 1.17 (95 % CI 1.16-1.18). An increase was also seen when we looked specifically for the use of SSRIs in at least the first trimester (IRR = 1.18, 95 % CI 1.17-1.20). An increased IRR in the use of drugs for pulmonary disease was also seen when children were exposed to TCAs, but this was not statistically significant. However, in both groups our sample size was rather small. The effect size is modest and may also be confounded by maternal smoking. CONCLUSIONS: In utero exposure to SSRIs leads to a statistically significant increase in the use of drugs for pulmonary diseases, especially when exposure occurred during the first trimester of pregnancy. The increase in the use of drugs for pulmonary disease may also be related to other factors. Therefore, further study is recommended.