Sex Differences in Antidepressant-Like Effect of Escitalopram and Venlafaxine

Clinical evidence indicates that there are sex differences in the risk of developing depressive disorders and in the effectiveness of various antidepressants in treating depression. However, the specific sex-dependent efficacy of escitalopram and venlafaxine remains unclear. The primary objective of this study is to investigate the sex differences in the antidepressant efficacy of escitalopram and venlafaxine, as well as to elucidate the underlying mechanisms. The forced swimming test (FST) was conducted to assess depression-like behavior, with subsequent analysis of neurotransmitter concentrations and related metabolites within the noradrenaline (NA) and serotonin (5-HT) systems in the prefrontal cortex (PFC) and hippocampus (HP) following treatment with escitalopram or venlafaxine. Surprisingly, the findings of this study indicate that both female and male mice display similar depressive-like behavior in the FST. Additionally, the data suggest that both escitalopram and venlafaxine are effective in reducing depressive-like behavior in mice regardless of sex, with females showing greater sensitivity to escitalopram. Furthermore, escitalopram was found to primarily affect the 5-HT system in females. Interestingly, the sex-specific effects of venlafaxine were linked to both the NA and 5-HT systems, despite the lack of evident differences in the FST results. In summary, our research has elucidated the sex-specific effects of escitalopram and venlafaxine. Understanding these differences and commonalities might shed light into informing tailored diagnostic and treatment intervention strategies.