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Abstract: venlafaxine%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>toludesvenlafaxine, a novel serotonin-norepinephrine-dopamine reuptake inhibitor, has shown promise in treating depression, yet direct comparisons with venlafaxine, a standard serotonin-norepinephrine reuptake inhibitor, remain limited, especially in the anhedonia facet. To address this gap, an 8-week multicenter, open-label, randomized controlled trial was conducted to compare venlafaxine%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>toludesvenlafaxine with venlafaxine as monotherapies for major depressive disorder (MDD). Assessments were performed at baseline and weeks 2, 4 and 8, including evaluations of anhedonia (Snaith-Hamilton Pleasure Scale (SHAPS) and Dimensional Anhedonia Rating Scale (DARS)), general depressive symptoms (Montgomery-?sberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating Scale (HAMD-17), and Self-Rating Depression Scale (SDS)), quality of life (Satisfaction Questionnaire-Short Form (Q-LES-Q-SF)), as well as safety (Treatment Emergent Symptom Scale (TESS)) and sexual function (Arizona Sexual Experience Scale (ASEX)). The results showed that, compared with venlafaxine, venlafaxine%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>toludesvenlafaxine had an earlier onset of action at week 2 in improving MADRS and HAMD-17 scores, along with alleviating anhedonia and suicidal ideation. At week 8, however, the SHAPS scores were comparable between the two groups, indicating their similar efficacy in treating anhedonia. In terms of safety, venlafaxine%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>toludesvenlafaxine exhibited significantly lower levels of triglycerides and total bilirubin, while other indices demonstrated no significant difference. Overall, both drugs showed comparable efficacy and safety profiles for MDD over the 8-week treatment period, with venlafaxine%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>toludesvenlafaxine potentially acting more rapidly.