Antidepressants and Antipsychotics in Human Pregnancy: Transfer Across the Placenta and Opportunities for Modeling Studies

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Abstract
There is limited information about the transfer of antidepressants and antipsychotics across the human placenta. The objective of the current review was to systematically screen the scientific literature using relevant keywords to collect quantitative data on placental transfer of these drugs in humans and to give an overview of current modeling approaches used in this context. The collected data encompassed clinically measured fetal:maternal (F:M) concentration ratios (ie, the ratio between drug concentrations measured in the umbilical cord and drug concentrations measured in the mother) and transfer data obtained from ex vivo cotyledon perfusion experiments. These data were found for 18 antidepressants and some of their pharmacologically active metabolites, and for 10 antipsychotics and the metabolites thereof. Based on the collected data, similar maternal and fetal exposure could be observed for only a few compounds (eg, norfluoxetine and desvenlafaxine), whereas for most drugs (eg, paroxetine, sertraline, and quetiapine), fetal exposure appeared to be on average lower than maternal exposure. Venlafaxine appeared to be an exception in that the data indicated equivalent or higher concentrations in the umbilical cord than in the mother. Physiologically based pharmacokinetic (PBPK) models were sporadically used to investigate maternal pharmacokinetics of antidepressants or antipsychotics (eg, for sertraline, aripiprazole, and olanzapine), although without explicitly addressing fetal drug exposure. It is recommended that PBPK modeling is applied more frequently to these drugs. Although no substitute for clinical studies, these tools can help to better understand pregnancy‐induced pharmacokinetic changes and ultimately contribute to a more evidence‐based pharmacotherapy of depression and psychosis in pregnant subjects.

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