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

Ramsteijn, A. S., Van de Wijer, L., Rando, J., van Luijk, J., Homberg, J. R. & Olivier, J. D. A., Jul-2020, In : Neuroscience and Biobehavioral Reviews. 114, p. 53-69 17 p.

Research output: Contribution to journalReview articleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)53-69
Number of pages17
JournalNeuroscience and Biobehavioral Reviews
Early online date19-Apr-2020
Publication statusPublished - Jul-2020


  • 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, DEVELOPMENTAL FLUOXETINE EXPOSURE, MATERNAL ANTIDEPRESSANT USE, AUTISM SPECTRUM DISORDER, DEPRESSIVE-LIKE BEHAVIOR, HIPPOCAMPAL BDNF GENE, EARLY-LIFE EXPOSURE, FORCED SWIM TEST, PRENATAL EXPOSURE, ADULT MALE, SEXUAL-DIFFERENTIATION

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