Safety in treatment: Classical pharmacotherapeutics and new avenues for addressing maternal depression and anxiety during pregnancy

We aimed to review clinical research on the safety profiles of antidepressant drugs and associations with maternal depression and neonatal outcomes. We focused on neuroendocrine changes during pregnancy and their effects on antidepressant pharmacokinetics. Pregnancy-induced alterations in drug disposition and metabolism impacting mothers and their fetuses are discussed. We considered evidence for the risks of antidepressant use during pregnancy. Teratogenicity associated with ongoing treatment, new prescriptions during pregnancy, or pausing medication while pregnant was examined. The Food and Drug Administration advises caution regarding prenatal exposure to most drugs, including antidepressants, largely owing to a dearth of safety studies caused by the common exclusion of pregnant individuals in clinical trials. We contrasted findings on antidepressant use with the lack of treatment where detrimental effects to mothers and children are well researched. Overall, drug classes such as selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors appear to have limited adverse effects on fetal health and child development. In the face of an increasing prevalence of major mood and anxiety disorders, we assert that individuals should be counseled before and during pregnancy about the risks and benefits of antidepressant treatment given that withholding treatment has possible negative outcomes. Moreover, newer therapeutics, such as ketamine and K-opioid receptor antagonists, warrant further investigation for use during pregnancy. Significance Statement: The safety of antidepressant use during pregnancy remains controversial owing to an incomplete understanding of how drug exposure affects fetal development, brain maturation, and behavior in offspring. This leaves pregnant people especially vulnerable, as pregnancy can be a highly stressful experience for many individuals, with stress being the biggest known risk factor for developing a mood or anxiety disorder. This review focuses on perinatal pharmacotherapy for treating mood and anxiety disorders, highlighting the current knowledge and gaps in our understanding of consequences of treatment. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).