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Therapeutic drug monitoring of psychoactive drugs during pregnancy in the genomic era: challenges and opportunities

Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA

Zachary N. Stowe

Women's Mental Health Program, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA

Jennifer L. Donovan

Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA

D. Jeffrey Newport

Page B. Pennell

James C. Ritchie

Michael J. Owens

Women's Mental Health Program, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA

Jun-Sheng Wang

Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA

Various symptoms of mental illness occur commonly during pregnancy. It is estimated that serious mental disorders, including major depression, bipolar disorder, schizophrenia, panic and other anxiety disorders, occur with a frequency of 10 to 25% in community samples of US women in their child-bearing years. As a result, approximately a third of all women take at least one psychoactive drug during pregnancy. Fetal drug exposure has been documented for all psychoactive drugs studied to date. However, the rate and extent of placental transfer within and between psychoactive drug classes remains ill defined. The contribution of various genetic factors such as the role of polymorphic drug metabolizing enzymes and drug transporters in controlling the variability of fetal drug exposure is also unclear. Therapeutic drug monitoring (TDM) has traditionally played an important role in psychiatric pharmacotherapy during pregnancy to ensure an adequate drug dose to achieve desired benefits while avoiding excessive fetal accumulation for drugs. In the genomic era, individualized treatment with specific drugs tailored to the mother's and fetus's genotype should eventually become the standard of care. Several methodological problems need to be overcome for this prediction to become reality. One approach to this goal taken by the Specialized Center of Research on Sex and Gender Factors Affecting Women's Health at the Emory University Women's Mental Health Program is described. This research is grounded on TDM of pregnant women receiving antidepressants, antipsychotics, anti-epileptic drugs and mood stabilizers. The use of pharmacokinetic and pharmacogenetic models to predict maternal plasma drug concentrations, fetal drug exposure, and maternal and neonatal outcomes, is expected to improve our understanding of dose-response relationships of psychoactive drugs in pregnancy.

Key Words: pregnancy • pharmacogenetics • P-glycoprotein • depression

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