Effects of chronic fluoxetine treatment on anxiety- and depressive-like behaviors in adolescent rodents – systematic review and meta-analysis

Abstract Background Drugs prescribed for psychiatric disorders in adolescence should be studied very extensively since they can affect developing and thus highly plastic brain differently than they affect the adult brain. Therefore, we aimed to summarize animal studies reporting the behavioral consequences of chronic exposure to the most widely prescribed antidepressant drug among adolescents i.e., fluoxetine. Methods Electronic databases (Medline via Pubmed, Web of Science Core Collection, ScienceDirect) were systematically searched until April 12, 2022, for published, peer-reviewed, controlled trials concerning the effects of chronic fluoxetine administration vs. vehicle on anxiety and depression measures in naïve and stress-exposed adolescent rodents. All of the relevant studies were selected and critically appraised, and a meta-analysis of eligible studies was performed. Results A total of 18 studies were included in the meta-analysis. In naïve animals, chronic adolescent fluoxetine administration showed dose-related anxiogenic-like effects, measured as a reduction in time spent in the open arms of the elevated plus maze. No significant effects of chronic adolescent fluoxetine on depression-like behavior were reported in naïve animals, while in stress-exposed rodents chronic adolescent fluoxetine significantly decreased immobility time in the forced swim test compared to vehicle. Conclusions These results suggest that although chronic fluoxetine treatment proves positive effects in animal models of depression, it may simultaneously increase anxiety in adolescent animals in a dose-related manner. Although the clinical implications of the data should be interpreted with extreme caution, adolescent patients under fluoxetine treatment should be closely monitored.