Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-Release Tablets in Depression With Anhedonia: A Single-Arm, Multicenter Clinical Study.

Toludesvenlafaxine hydrochloride sustained-release tablets, as China's first independently developed chemical Class 1 innovative drug with independent intellectual property rights for the treatment of depression and a new molecular entity, represent a novel triple reuptake inhibitor (TRI) with specific target selectivity for serotonin (5-HT), norepinephrine (NE), and dopamine (DA). This single-arm, multicenter clinical study aimed to evaluate the efficacy and safety of toludesvenlafaxine in alleviating anhedonia symptoms in patients with major depressive disorder (MDD). A total of 123 patients aged 18-65 years were enrolled between April 2023 and April 2024 and received an 8-week treatment with toludesvenlafaxine sustained-release tablets (80-160 mg/day). The primary efficacy endpoint was the change in the total score of the Dimensional Anhedonia Rating Scale (DARS) at weeks 2, 4, and 8. Significant improvements in DARS scores were observed, with mean changes from baseline of 8.4 (95% CI [6.4, 10.4], < 0.0001), 14.1 (95% CI [12.0, 16.2], < 0.0001), and 20.4 (95% CI [18.0, 22.9], < 0.0001), respectively. Additionally, after 8 weeks of treatment, plasma levels of neurotrophic factors, including mature brain-derived neurotrophic factor (mBDNF) ( = 28.78, < 0.0001), pro-BDNF ( = 27.71, < 0.0001), and vascular endothelial growth factor (VEGF) ( = 31.07, < 0.0001), were significantly increased, and the plasma level of IGF-1 was not significantly changed ( = 0.35, =0.7269). No association was found between the percentage of changes in neurotrophic factors and the percentage of symptom improvements. Toludesvenlafaxine was generally well-tolerated, with treatment-emergent adverse events (AEs) (TEAEs) reported in 83.7% of participants and treatment-related AEs (TRAEs) in 76.4%. These findings indicate that toludesvenlafaxine hydrochloride sustained-release tablets are safe, well-tolerated, and effective in alleviating anhedonia symptoms in patients with depression. http://www.chictr.org.cn (No.: ChiCTR2300070331).