Treatment With Antipsychotics in Pregnancy: Changes in Drug Disposition

Abstract

Although pregnancy is known to cause changes in drug pharmacokinetics, little is known about its impact on serum levels of antipsychotics. In this study we retrospectively assessed 201 routine serum antipsychotic therapeutic drug monitoring concentration measurements obtained from a total of 110 pregnancies in 103 women, and 512 measurements from the same women before and after pregnancy. Serum concentrations in the third trimester were significantly lower than baseline for quetiapine (−76%; confidence interval (CI), −83%, −66%; P < 0.001) and aripiprazole (−52%; CI, −62%, −39%; P < 0.001), but not for olanzapine (−9%; CI, −28%, +14%; P = 0.40). For the remaining antipsychotics (perphenazine, haloperidol, ziprasidone, risperidone, and clozapine), our dataset was limited, but it indicates that concentrations may decline at least for perphenazine and possibly also for haloperidol. Even though the clinical consequence of the serum concentrations decline remains to be elucidated, our results warrant close clinical monitoring throughout pregnancy, preferentially supported by therapeutic drug monitoring.

Quetiapine dose optimisation during gestation: a pharmacokinetic modelling study

“…Simulations were run for the entire gestation period (38 weeks) with sampling of the first day on each week for every 5 weeks reported (Figure ). For non‐pregnant subjects (baseline), model‐predicted plasma concentrations (54.59 ng/ml ± 26.98 ng/ml) were within twofold of those reported by Westin et al (75.6 ng/ml; Table ), while also spanning across a similar range. Westin et al reported a 22, 57 and 76% decrease in mean plasma concentration at for trimesters 1, 2 and 3, respectively.…”

“…A recent report by Westin et al examined the plasma concentrations of antipsychotics during gestation from retrospective analysis of therapeutic drug monitoring (TDM) clinical data from Norway. They identified that quetiapine and aripiprazole exhibited a significant decrease in plasma concentrations during gestation, by between 50 and 80% by trimester 3.…”

“…To our knowledge, Westin et al is the only publication (to date) containing quetiapine plasma concentrations throughout gestation and this was used as the basis for validating the quetiapine pregnancy PBPK model. Simulations were run for the entire gestation period (38 weeks) with sampling of the first day on each week for every 5 weeks reported (Figure ).…”

“…A recent report by Westin et al retrospectively collated serum level of antipsychotics before, during and after pregnancy. Data for quetiapine consisted of 66 measurements during pregnancy, 11 during the first 12 weeks following pregnancy and 144 at baseline, from 33 women.…”

“…In a recent retrospective study, the plasma levels of a range of antipsychotics were analysed during gestation and it was identified that significant decreases in serum levels were evident, particularly for quetiapine, which decreased by up to 70% in trimester 3 …”