Comparative efficacy of non-pharmacological therapies in adolescents with subthreshold depression: a systematic review and network meta-analysis.

BACKGROUND

Subthreshold depression (SD) is highly prevalent in adolescents and young adults aged 11-25 years, leading to impaired psychosocial functioning and a high risk of progression to major depressive disorder (MDD). Non-pharmacological therapies are the mainstay of intervention for adolescent SD, yet the comparative efficacy of different interventions remains unclear. This study aimed to compare the relative effectiveness of various non-pharmacological interventions for adolescent SD via network meta-analysis (NMA).

METHODS

We initially retrieved 5,297 records from six databases (PubMed, Embase, Web of Science, Cochrane, PsycINFO, CINAHL) for randomized controlled trials (RCTs) of non-pharmacological interventions for SD in individuals aged 11-25 years who did not meet the DSM-IV/ICD-10 diagnostic criteria for MDD or depressive episode. The control groups received waitlist control or usual care, and the primary outcome was depressive symptoms assessed by validated scales (BDI-II, CES-D, CDI, HAMD). Two reviewers independently conducted study selection, data extraction and risk of bias assessment (RoB 2.0). Heterogeneity was analyzed using the I² statistic; NMA was performed under a Bayesian framework with consistency assessment, and the CINeMA tool was used to grade the certainty of evidence. This study was registered in PROSPERO (CRD42023456264) and reported in accordance with the PRISMA 2020 statement.

RESULTS

A total of 30 RCTs involving 3,471 participants were included. Traditional meta-analysis showed that non-pharmacological interventions significantly improved depressive symptoms in adolescents with SD (pooled SMD = -0.93, 95% CI: -1.20 to -0.66, P < 0.0001), with high heterogeneity across studies (I² = 92%) driven by intervention type, delivery mode, intervention duration and participant age. NMA results indicated that behavioral activation (BA) was the most effective intervention (SMD = -3.45, 95% CI: -4.89 to -2.02), followed by physical exercise intervention (PEI) (SMD = -1.34, 95% CI: -2.68 to -0.03) and light therapy (LT) (SMD = -1.24, 95% CI: -2.17 to -0.31). No significant overall inconsistency was detected in the study (χ²=6.72, df=9, P = 0.651).

CONCLUSIONS

Non-pharmacological interventions are effective for adolescents with SD, and BA is recommended as the first-line clinical option. Clinical selection of interventions should take into account individual patient characteristics and intervention features. This study has several limitations, including high heterogeneity across studies, single-study evidence for some interventions (e.g., LT, PEI), a broad age range of participants and the lack of long-term follow-up data. Further large-scale, multi-center RCTs are needed to validate these findings.