Optimising antidepressant therapy in pregnancy: a perspective on therapeutic drug monitoring and model-informed precision dosing

Depression during pregnancy is common worldwide, with higher prevalences in low-income countries compared to high-income countries. Yet, current antidepressant dosing strategies in pregnant patients rarely account for the substantial pharmacokinetic shifts that occur. Altered hepatic metabolism and enhanced renal clearance can reduce plasma concentrations, potentially compromising efficacy. Therapeutic drug monitoring (TDM) offers one strategy: targeting plasma concentrations that correlate with adequate central nervous system (CNS) target engagement. Model-informed precision dosing (MIPD) takes this further, using population pharmacokinetic modelling to predict individualised doses. We examined prescribing patterns in an IRB-approved retrospective cohort and observed that dosing remained stable across trimesters despite reported pharmacokinetic alterations. This disconnect between emerging pharmacological knowledge and current practice deserves attention. Challenges remain such as assay availability is limited, there are fundamental cost considerations, and pregnancy-specific reference ranges need further development. Our position is that interdisciplinary collaboration should drive the growth of standardised protocols that integrate TDM and MIPD into prenatal care. Prospective trials will ultimately establish clinical benefit, but the mechanistic rationale already warrants systematic investigation.