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

A. S. Ramsteijn, L. Van de Wijer, J. Rando, J. van Luijk, J. R. Homberg*, J. D.A. Olivier

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

26 Citations (Scopus)
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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

Bibliographical note

Funding Information:
This work was supported by a ZonMw grant (MKMD project; ID 114024127 ) awarded to JO & AR, and a grant awarded to JH from the Donders Institute for Brain, Cognition and Behavior . Funding bodies had no role in study design, data collection, data analysis, data interpretation, or the writing of the report.


  • 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


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