Toludesvenlafaxine Hydrochlorid

Depression negatively impacts the prognosis of various cancers, including lung cancer, by influencing antitumor immune responses and impairing immune cell function. Antidepressants may modulate the tumor immune microenvironment, enhancing immunotherapy efficacy. However, the specific mechanisms remain unclear. This study investigates the effects of the antidepressant Ansofaxine on immune therapy in non-small cell lung cancer (NSCLC) mice with comorbid depression.

Chronic unpredictable mild stress (CUMS) and Lewis lung cancer cells (LLC) model was established in mice. Ansofaxine and a combination of triple immunotherapy (anti-PD-1, anti-TNFR2, and anti-PTP1B) were treated in mice to monitor tumor growth and survival rates. Flow cytometry and immunohistochemistry were employed to analyze the dynamics of the immune system, while ELISA kits were used to quantify neurotransmitter levels.

Depression accelerated NSCLC progression, evidenced by increased tumor volume, spleen size, and reduced survival rates. Flow cytometry analysis demonstrated a reduction in the population of immune effector cells, with an increase in the proportion of immunosuppressive cells. Ansofaxine inhibited LLC cell proliferation and migration, enhancing apoptosis more effectively than venlafaxine and fluoxetine. Combined with triple immunotherapy, Ansofaxine improved survival rates and enhanced immune responses, increasing CD8⁺ T cell proportions and decreasing Tregs. Ansofaxine also restored serum serotonin and norepinephrine levels in depressed mice, reduced corticosterone, and decreased PD-L1 and TNFR2 expression in tumor tissues.

The findings suggest that Ansofaxine may represent a promising therapeutic approach for NSCLC patients with comorbid depression, potentially enhancing both mental well-being and cancer-related outcomes.

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], p < 0.0001), 14.1 (95% CI [12.0, 16.2], p < 0.0001), and 20.4 (95% CI [18.0, 22.9], p < 0.0001), respectively. Additionally, after 8 weeks of treatment, plasma levels of neurotrophic factors, including mature brain‐derived neurotrophic factor (mBDNF) ( t  = 28.78, p < 0.0001), pro‐BDNF ( t  = 27.71, p < 0.0001), and vascular endothelial growth factor (VEGF) ( t  = 31.07, p < 0.0001), were significantly increased, and the plasma level of IGF‐1 was not significantly changed ( t  = 0.35, p = 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. Trial Registration:http://www.chictr.org.cn (No.: ChiCTR2300070331).