نبذة مختصرة : Objectives. To assess the cost-effectiveness of an economic empowerment and family intervention on mental health outcomes among school-going adolescent girls in Uganda from 2017 to 2022. Methods. We randomized adolescent girls aged 14 to 17 years into 3 arms: (1) health and sex education (usual care; n = 408), (2) youth development accounts (YDAs; n = 471), and (3) a combination intervention (YDA plus multiple family group [MFG]; n = 381). We fitted mixed-effects models and estimated intervention costs prospectively using the microcosting approach. Results. The combination intervention had a statistically significant impact on mental health outcomes (depressive symptoms, hopelessness, self-concept) at 12 and 24 months, except self-esteem at 24 months, relative to usual care, with incremental cost‒effectiveness ratios ranging from $51 to $100 per 0.2-SD change at 12 months, and $53 to $157 at 24 months per 0.2-SD change. Conclusions. The combination intervention positively and significantly impacted a higher number of mental health outcomes among school-going adolescent girls compared with YDA alone. The benefits were sustained in the short and long term, with the incremental cost-per-unit effect remaining comparable. Findings support the integration of combination interventions in school settings to promote adolescent girls’ positive mental health functioning. Trial Registration. ClinicalTrials.gov registration no. NCT03307226. ( Am J Public Health. Published online ahead of print June 26, 2025:e1–e9. https://doi.org/10.2105/AJPH.2025.308135 )
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