Changes in S‐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.