by APAL Co-Director Kathryn Emerick, MD
Throughout gestation, pregnant individuals experience numerous physiological changes. In perinatal psychiatry, the foremost considerations revolve around alterations in drug distribution and metabolism. During pregnancy, there is an increase of the maternal plasma volume which reaches a 50% increase during third trimester.
The ratio of lean muscle to adipose tissue is decreased and both renal blood flow and glomerular filtration rate (GFR) increase. These changes are significant as they ultimately lead to a likely lower peak plasma concentration of medication, despite the possibility of an increased free fraction of drugs due to lower albumin levels.
Additionally, there are notable changes in hepatic metabolism during pregnancy including increase in activity of CYP enzymes 3A4, 2A6, 2D6, UGT1A4 and possibly UGT2B7. This alteration is important because these enzymes are responsible for the metabolism of a majority of psychiatric medications including SSRIs, SNRIs, benzodiazepines, first and second generation antipsychotics and certain TCAs.
The takeaway here is to remember that treating to remission is a core tenant of perinatal psychiatry and that means continuing to assess for medication response throughout pregnancy. We know that the same dose can be effectively lower as pregnancy progresses and pregnant people may report the dose that worked for them prior to pregnancy is no longer as effective.
Sources
Chisolm MS, Payne JL. Management of psychotropic drugs in pregnancy and lacation. Int J Psychiatry Med. 1994; 24:129-47.
Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy- a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2006; 20:64-9.
Orsolini, Laura & Uguz, Faruk. (2019). Perinatal Psychopharmacology. 10.1007/978-3-319-92919-4.