Perinatal selective serotonin reuptake inhibitor exposure and behavioral outcomes: A systematic review and meta-analyses of animal studies

Abstract

In the Western world, 2-5 % of pregnant women use selective serotonin reuptake inhibitor (SSRI) antidepressants. There is no consensus on the potential long-term neurodevelopmental outcomes of early SSRI exposure. Our aim was to determine whether there is an overall effect of perinatal SSRI exposure in animals on a spectrum of behavioral domains. After a comprehensive database search in PubMed, PsycINFO, and Web of Science, we included 99 publications. We performed nine meta-analyses and two qualitative syntheses corresponding to different behavioral categories, aggregating data from thousands of animals. We found evidence for reduced activity and exploration behavior (standardized mean difference (SMD) -0.28 [-0.38, -0.18]), more passive stress coping (SMD -0.37 [-0.52, -0.23]), and less efficient sensory processing (SMD -0.37 [-0.69, -0.06]) in SSRI- versus vehicle-exposed animals. No differences were found for anxiety (p = 0.06), social behavior, learning and memory, ingestive- and reward behavior, motoric behavior, or reflex and pain sensitivity. Exposure in the period equivalent to the human third trimester was associated with the strongest effects.

Keywords: Activity and exploration; Animal studies; Antidepressants; Anxiety; Behavior; Developmental exposure; Ingestive and reward behavior; Learning and memory; Meta-analysis; Motoric behavior; Offspring; Pregnancy; Reflex and pain sensitivity; Selective serotonin reuptake inhibitors (SSRIs); Sensory processing; Sleep and circadian activity; Social behavior; Stress coping; Systematic review; Teratogenic effects.