Comparative efficacy and acceptability of non-invasive brain stimulation and acupuncture for depression: protocol for a systematic review and network meta-analysis

Introduction Depression is a significant global health burden, affecting over 300 million people worldwide and contributing substantially to disability and healthcare costs. Despite the widespread use of antidepressants, many patients experience limited efficacy or adverse effects. Non-invasive brain stimulation (NIBS) and acupuncture have emerged as promising non-pharmacological interventions for depression. However, the heterogeneity of treatment protocols and the lack of direct comparisons limit the development of optimal treatment strategies. This study seeks to perform a network meta-analysis (NMA) to compare and rank the comparative efficacy and acceptability of NIBS and acupuncture interventions for depression. This review is expected to inform evidence-based decision-making by comparatively evaluating efficacy and acceptability; any clinical implications will depend on the certainty and consistency of the evidence. Methods and analysis A comprehensive literature search will be conducted across 14 academic databases and registries (PubMed, Cochrane Library, Web of Science, Embase, OVID, Scopus, ProQuest, CNKI, Wanfang, CBM, VIP, ICTRP, ChiCTR and ClinicalTrials.gov) from inception to May 2025. Eligible studies will include randomised controlled trials assessing NIBS and/or acupuncture for depression. Two reviewers will independently conduct study selection, data extraction and risk of bias assessment using the Cochrane Risk of Bias 2 tool. Primary outcomes will include depressive symptom severity and acceptability (measured by all-cause discontinuation). Secondary outcomes will include response rate and adverse events. At the time of protocol submission, the literature search had been substantially completed, while study selection and data extraction had not yet commenced. Pairwise meta-analyses will be executed applying Review Manager V.5.4 and Stata V.17.0. A Bayesian NMA will be conducted via the GeMTC package in R V.4.2.2, and Stata will also be used for additional statistical analyses and visualisation. Subgroup and sensitivity analyses will explore sources of heterogeneity, and the certainty of evidence will be appraised using the Confidence in Network Meta-Analysis framework. Ethics and dissemination Ethical approval is not warranted since the study does not involve any confidential or private patient records. The results will be disseminated through publication in peer-reviewed journals. PROSPERO registration number CRD420250651706.