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

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.HighlightsPerinatal SSRI exposure in rodents alters outcomes in three behavioral domains.It leads to reduced activity, passive stress coping, and weaker sensory processing.Females are understudied but seem to be less vulnerable than males.Early postnatal exposure in rodents leads to the largest effects on behavior.This is equivalent to the third trimester of pregnancy in humans.