Efficacy and Mechanism of Acupuncture for Depression in Adolescents: Protocol for a Prospective, Multi-center, Randomized Controlled Trial Study

Background Adolescent depression presents a significant public health concern, with current pharmacological interventions raising efficacy and safety considerations. While acupuncture has demonstrated therapeutic efficacy in adult depression, its mechanisms of action and therapeutic potential in adolescent populations remain understudied. This study aims to evaluate acupuncture’s efficacy and safety profile in treating adolescent depression through a multidimensional analysis encompassing sex hormones, neurotransmitter systems, proteomics, fMRI, and salivary BDNF. The findings may elucidate potential biomarkers and therapeutic mechanisms, thereby establishing an evidence base for early diagnostic strategies and clinical implementation of acupuncture-based interventions in adolescent depression. Methods This study was a randomized, multi-center, double-blind, placebo-controlled clinical trial involving six sub-centers. A total of 360 patients and 20 healthy subjects were included. The patients were randomly assigned to the acupuncture group and the sham acupuncture group at a ratio of 1 : 1. Both groups received acupuncture intervention three times a week for a total of 4 weeks. Healthy subjects were only extracted serum for comparative analysis of proteomics. Results : HAMD-24 reduction rate was used as the main indicator, PSQI and ESS scores as secondary indicators, sex hormone levels, neurotransmitters (dopamine, 5-HT, GABA, Glu, Ach, NE) levels and differential protein expression, DNA methylation level of salivary BDNF promoter region, and head fMRI were used as mechanism research indicators. Discussion This is a multi-center, large sample, prospective, double-blind, randomized controlled trial.In this study, the placebo effect of acupuncture was better excluded by taking the same acupuncture point flat head acupuncture sham acupuncture. The pathogenesis of this unique group of adolescents was analyzed from the level of sex hormones, and the differential protein expression was studied by proteomics analysis. Combined with sex hormones, serum neurotransmitters, DNA methylation level of saliva BDNF promoter region, head fMRI changes, and other neuroendocrine indicators before and after acupuncture, multi-dimensional intervention mechanisms and biomarkers were explored. Trial registration International Traditional Medicine Clinical Trial Registry, ITMCTR2025000479, Date registered: 6 March 2025.