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