Trimesters induced changes in pharmacokinetic parameters of antipsychotics

There is a need to balance maternal mental health treatment with fetal safety when prescribing antipsychotic medications during pregnancy. Physiological changes during pregnancy markedly influence drug pharmacokinetics, making it difficult to achieve therapeutic efficacy without compromising on the risks.

A systematic review was performed to identify trimester-specific physiological changes impacting antipsychotic pharmacokinetics. A retrieval of relevant studies published between inception to October 3, 2023 was conducted through PubMed, Web of Science, Cochrane Library, and Embase. Key pharmacokinetic parameters examined include bioavailability, volume of distribution, clearance, half-life, and area under the curve.

Pregnancy-related physiological changes, such as increased plasma volume, enhanced hepatic blood flow, and altered protein binding, can significantly affect the pharmacokinetics of antipsychotics. For instance, plasma concentrations of Haloperidol, a first generation antipsychotic (FGA), have been reported to decrease by up to 52% in the third trimester. Similarly, Quetiapine and Aripiprazole, both second generation antipsychotics (SGAs), show substantial reductions in plasma levels during the same period, by 76.2% and 76.8%, respectively. These findings suggest a potential need for dose adjustments to maintain therapeutic drug exposure as pregnancy progresses. Physiologically based pharmacokinetic (PBPK) models further support this adjustment to ensure continued clinical efficacy.

Significant changes in pharmacokinetics are observed for antipsychotic drugs during pregnancy, underlining the importance of developing a personalized dosing strategy and therapeutic drug monitoring to maximize therapeutic efficacy and at the same time keep the treatment safe for mother and fetus.