Abstract: Subthreshold depression (StD) is a highly prevalent condition in adolescents at high-risk of developing Major depressive disorder (MDD). Lycium barbarum polysaccharide (LBP), extracted from Lycium barbarum (L. barbarum), has demonstrated potential antidepressant effects including but not limited to anti-oxidative and anti-inflammatory properties in preclinical models of neurological and psychiatric diseases. The effect of LBP on StD is, however, not known. This study investigated whether LBP treatment alleviated depressive symptoms in adolescents with StD. In this randomized, double-blind, placebo-controlled trial (RCT), 29 adolescents with StD were randomly assigned to receive LBP 300 mg daily or placebo for 6 weeks. Intervention effects were assessed at weeks 4 and 6. The primary outcome was changes in score of the Hamilton Depression Scale (HAMD-24) from baseline to week 6. The secondary was changes in score of the Beck Depression Inventory-II (BDI-II), The Pittsburgh Sleep Quality Index (PSQI), The Kessler Psychological Distress Scale (Kessler) and Screen for Child Anxiety-Related Emotional Disorders (SCARED). Tolerability and safety were assessed via Treatment Emergent Symptom Scale (TESS). The data for an interim analysis were collected before 30 October 2020 and included all participants who completed a 6-weeks course of treatment. A total of 29 participants were eligible and randomized to either LBP (n = 15) or placebo (n = 14) group. LBP-treated subjects showed a greater reduction in total HAMD-24 scores at week 6 compared to placebo (group difference: 3·193; 95% confidence interval (CI) = 0·675 to 5·710; F = 6·374; p = 0·014; Cohen’s d = 0·860). The LBP group showed a higher remission rate (defined as HAMD-24 total score ≤ 7) than placebo-controlled group (Bootstrap regression coefficient 2·476; 95% CI = 0·033–50·9; p = 0·03). No significant between-group differences were found in BDI-II, PSQI, Kessler and SCARED (p > 0.05). No side effects related to interventions were reported in either group. This 6-week RCT study provides preliminary evidence supporting LBP as an effective agent in reducing depressive symptoms in adolescents with StD. LBP is well tolerated with no treatment-limiting adverse events. Large clinical trials are warranted for further confirming the antidepressant effects of LBP in persons with StD and patients with MDD.

Key words: Subthreshold depression, Randomized Clinical Trial, Lycium barbarum polysaccharide, Efficacy, Side-effect