Pharmacokinetics of Antidepressants in Pregnancy

Abstract

Depression is common in pregnant women. However, the rate of antidepressant treatment in pregnancy is significantly lower than in nonpregnant women. Although some antidepressants may cause potential risks to the fetus, not treating or withdrawing the treatment is associated with relapsing and adverse pregnancy outcomes such as preterm birth. Pregnancy-associated physiologic changes can alter pharmacokinetics (PK) and may impact dosing requirements during pregnancy. However, pregnant women are largely excluded from PK studies. Dose extrapolation from the nonpregnant population could lead to ineffective doses or increased risk of adverse events. To better understand PK changes during pregnancy and guide dosing decisions, we conducted a literature review to catalog PK studies of antidepressants in pregnancy, with a focus on maternal PK differences from the nonpregnant population and fetal exposure. We identified 40 studies on 15 drugs, with most data from patients taking selective serotonin reuptake inhibitors and venlafaxine. Most of the studies have relatively poor quality, with small sample sizes, reporting concentrations at delivery only, a large amount of missing data, and not including times and adequate dose information. Only four studies collected multiple samples following a dose and reported PK parameters. In general, there are limited data available regarding PK of antidepressants in pregnancy and deficiencies in data reporting. Future studies should provide accurate information on drug dosing and timing of dose, PK sample collection, and individual-level PK data.

Keywords: antidepressants; fetal exposure; obstetrics; pharmacokinetics; special populations.