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.
Journal of Psychopharmacology (Impact Factor: 3.59). 08/2006; 20(4 Suppl):54-9. DOI: 10.1177/1359786806066054
Source: PubMed


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.

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    • "n placenta , the relationship between genetic polymorphisms of transporters and placental passage of drugs are far from clear . Contradictory data exist for the SNPs of P - gp and the expression and function of P - gp on its substrate ' s disposition . Studies are needed to evaluate the role of pharmacogenetic variables on placental drug passage ( DeVane et al . , 2006 ) . One obstacle in using genetic information prospectively to select psychoactive drugs for use in the pregnant patient is recognition that genotypes for placen - tal transporters are determined by the genetics of the fetus rather than the mother , thereby preventing the use of maternal tissue to genotype for placental transporters . I"
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    ABSTRACT: P-glycoprotein, breast cancer resistance protein, and multidrug resistance proteins have physiological functions in placental tissue. Several antidepressants, antipsychotics, and anti-epileptic drugs have been found to be substrates of P-glycoprotein and other transporters. The extent that drugs pass through the placental barrier is likely influenced by drug transporters. The rational choice of psychoactive drugs to treat mental illness in women of child-bearing age should incorporate knowledge of both drug disposition as well as expected pharmacologic effects. This review summarizes the current data on drug transporters in the placental passage of medications, with a focus on medications used in clinical psychopharmacology.
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