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

Background: YOXINTINE 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.

Purpose: To evaluate YOXINTINE in treating depression compared with a placebo in Chinese patients.

Study design: This was a multicenter, double-blinded, randomized, placebo-controlled, phase 2 clinical trial.

Methods: The 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.

Results: The 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.

Conclusion: Oral YOXINTINE is safe and significantly improves depressive symptoms. PPD may exhibit antidepressant properties through mechanisms distinct from monoamine reuptake inhibition.

Registration number: ChiCTR2300070568.