The impact of pregnancy on the pharmacokinetics of antidepressants: a systematic critical review and meta-analysis

Introduction: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A clearer understanding of pregnancy-related effects on antidepressant disposition may facilitate the development of guidelines for appropriate dose adjustments during the course of pregnancy based on therapeutic drug monitoring.Areas covered: We systematically reviewed studies comparing antidepressant levels in the same individuals during pregnant and non-pregnant states. Using dose-adjusted plasma concentration measurements, we estimated alteration ratios between the 3rd trimester and baseline (before or after pregnancy). Additionally, we performed a meta-analysis for changes in dose-adjusted concentrations to estimate mean differences.Expert opinion: Data for several antidepressants display clear alteration patterns during pregnancy. On the basis of the alteration ratios trimipramine, fluvoxamine, and nortriptyline show a prominent decrease in dose-adjusted levels, especially in the 3rd trimester. Clomipramine, imipramine, citalopram, and paroxetine show smaller decreases in dose-adjusted concentrations in the third trimester. For escitalopram, venlafaxine and fluoxetine, changes are considered negligible. For sertraline, there was a tendency toward increased dose-adjusted concentrations in pregnancy. Available evidence suffers from major limitations and factors affecting pharmacokinetics have been insufficiently addressed. Further research is required to promote knowledge on pregnancy effects on antidepressant pharmacokinetics.