Efficacy and safety of sini powder combined with Xiaoxianxiong decoction for adolescent depression with liver qi stagnation and phlegm-heat obstruction syndrome: a randomized controlled trial.

OBJECTIVE

To assess efficacy and safety of Sini San combined with Xiaoxianxiong Tang as add-on therapy for adolescents (12-18 years) with liver qi stagnation and phlegm-heat depression, and to provide preliminary evidence for TCM syndrome-based treatment.

METHODS

Sixty adolescents (12-18 years) with moderate depression (DSM-5 criteria) meeting TCM syndrome standards were recruited from Youxian Branch of Mianyang Third Hospital (Jan 2024-Dec 2025). Sample size was calculated via G*Power 3.1 (effect size=0.8, α=0.05, β=0.2). A conservative effect size of 0.6 for TCM add-on trials in adolescent depression required 44 participants per group. Our sample size was calculated using the commonly adopted large effect size (0.8) for such trials, which was adequate to detect the predefined clinically meaningful effect. Participants were randomly assigned to TCM decoction+psychological counseling (n = 30) or psychological counseling alone (n = 30) with allocation concealment, receiving 8-week intervention.Intention-to-treat (ITT) analysis with last observation carried forward (LOCF) for missing data was used. All outcomes were assessed by independent blinded evaluators. Primary outcomes: CDRS-R and TCM syndrome scores; secondary outcomes: PedsQL score, clinical effective rate, adverse events. Cohen's d and 95% CIs were calculated with Bonferroni correction for multiple comparisons.

RESULTS

Baseline characteristics were comparable between groups (all P > 0.05). After 4 and 8 weeks, both groups showed improved outcomes (all P < 0.001). At 8 weeks, the study group had lower CDRS-R (13.02 ± 3.25 vs. 21.85 ± 3.56, t = 10.23, P < 0.001, Cohen's d = 2.64, 95%CI:1.72-3.56), lower TCM syndrome scores (3.21 ± 1.35 vs. 6.98 ± 1.62, t = 9.87, P < 0.001, Cohen's d = 2.52, 95%CI:1.61-3.43), higher PedsQL scores (79.35 ± 7.61 vs. 66.89 ± 7.43, t = 6.54, P < 0.001, Cohen's d = 1.68, 95%CI:0.92-2.44), and higher clinical effective rate (90.0% vs. 63.3%, χ 2 = 6.67, P = 0.010, 95%CI:9.7%-43.3%). The study group reported 6.7% mild gastrointestinal discomfort, with no serious adverse events.

CONCLUSION

As an add-on therapy to psychological counseling, Sini San combined with Xiaoxianxiong Decoction shows preliminary short-term efficacy in alleviating depressive symptoms and improving quality of life in adolescents with target TCM syndrome, with favorable short-term safety. Due to small sample size, single-center design, lack of double-blinding and placebo control, the findings are hypothesis-generating and cannot support broad clinical promotion.