Can antidepressants compromise sperm quality? A comprehensive review of preclinical evidence

Infertility is a significant global health concern, particularly among individuals of reproductive age. At the same time, psychiatric disorders-especially depression and anxiety-are increasingly prevalent, leading to a growing global demand for antidepressants.

The present review aimed to compile and analyze preclinical studies evaluating the effects of antidepressant exposure on sperm parameters and fertility outcomes in animal models.

A comprehensive literature search was conducted in April 2023 using the PubMed/Medline, Web of Science, and Scopus databases. The search strategy combined terms such as "fertility," "sperm," and "semen" with keywords related to various classes of antidepressants and their specific compounds. Eligible studies included experimental research assessing sperm and/or fertility parameters following antidepressant administration in male animals. Data extracted from the selected studies included drug class, specific compound, dosage, treatment duration, animal species, subject age, and reproductive outcomes.

A total of 32 studies met the inclusion criteria. Among the antidepressants investigated, selective serotonin reuptake inhibitors were the most frequently studied, with venlafaxine, fluoxetine, and paroxetine being the most commonly evaluated compounds. Most studies reported adverse effects on sperm parameters, such as concentration, motility, and morphology. However, evidence regarding fertility outcomes remains inconclusive due to the limited number of studies and considerable heterogeneity in experimental designs and treatment protocols.

These findings suggest that several antidepressants may impair sperm quality in animal models, with possible implications for male fertility. Nonetheless, further research is warranted to clarify these effects, particularly for less-studied antidepressant classes.