Efficacy and safety of YOXINTINE for depression: A double-blinded, randomized, placebo-controlled, phase 2 clinical trial

Abstract

BackgroundYOXINTINE contains >98 % of 20(S)-protopanaxadial (PPD), a metabolic product of ginsenosides with pre-clinical neuroprotective activity. Animal experiments and previous studies have shown that PPD has good antidepressant effect and safety. PurposeTo evaluate YOXINTINE in treating depression compared with a placebo in Chinese patients. Study DesignThis was a multicenter, double-blinded, randomized, placebo-controlled, phase 2 clinical trial. MethodsThe study included 178 randomized (1:1:1) Chinese patients with depression. Patients were randomly assigned to receive oral YOXINTINE at doses of 200 or 400 mg or a placebo administered twice daily for 8 weeks. The primary outcome was assessed by measuring changes in the Montgomery–Asberg Depression Rating Scale (MADRS) total score. All adverse reactions were recorded. All demographic and baseline characteristics were comparable. ResultsThe changes in MADRS total scores from baseline were −10.43 for the placebo group, −16.24 for the 200 mg YOXINTINE group, and −13.60 for the 400 mg YOXINTINE group. The differences in MADRS total score changes compared with the placebo were −5.81 (95 % CI: −7.69, −3.92; P < 0.0001) and −3.17 (95 % CI: −5.08, −1.25; P = 0.0013) for the 200 mg and 400 mg groups, respectively. The results indicated a significantly greater MADRS score reduction in the 200 mg group (P = 0.0058, 95 % CI: 0.78, 4.51). Adverse event incidence was comparable among all groups. ConclusionOral YOXINTINE is safe and significantly improves depressive symptoms. PPD may exhibit antidepressant properties through mechanisms distinct from monoamine reuptake inhibition. Registration numberChiCTR2300070568