Changes in <i>S</i>‐Citalopram Plasma Concentrations Across Pregnancy and Postpartum

Major depressive disorder is a common disorder in pregnancy. Although citalopram/escitalopram is the second most frequently prescribed antidepressant for pregnant people, information about its pharmacokinetics in pregnancy is limited. We investigated plasma (S)-citalopram concentration to dose (C/D) ratios across pregnancy and postpartum and the effect of pharmacogenetics on its elimination. This prospective observational cohort study enrolled 30 participants with a singleton pregnancy who chose to continue citalopram/escitalopram during pregnancy for a prior diagnosis of major depression. Monthly blood samples were obtained 24 hours post-dose across pregnancy and twice postpartum for measurement of plasma citalopram, desmethylcitalopram, and didesmethylcitalopram enantiomer concentrations. Compared with the 36-week reference, (S)-citalopram C/D ratios were not significantly different throughout pregnancy. However, the mean (S)-citalopram C/D ratio was elevated by 63% (P < 0.001) 6 to 8 weeks after delivery before it decreased to a mean C/D ratio in the later post-birth period that was marginally different than at 36 weeks (1.20 ± 0.64 vs. 0.92 ± 0.46, respectively; P = 0.06). Analyzing the results by cytochrome P 450 (CYP) 2C19 phenotype, the mean late postpartum (S)-citalopram concentration to dose ratio in intermediate metabolizers was approximately twice that in extensive, rapid, or ultrarapid metabolizers. However, at the 36-week reference point, the mean concentration to dose ratio in pregnant CYP2C19 intermediate metabolizers was 35.7% lower than the distant postpartum ratio, while the ratios in extensive and rapid/ultrarapid metabolizers were 15.4% and 18.5% lower, respectively. Without dose adjustment, people with intermediate or poor CYP2C19 activity may be at risk for subtherapeutic S-citalopram concentrations during pregnancy.