Comparative Efficacy of Non-invasive Brain Stimulation for Pain, Anxiety, and Depression: A Systematic Review and Network Meta-analysis
摘要
Although non-invasive brain stimulation (NIBS) has been used to manage chronic musculoskeletal pain (CMP) and related emotional symptoms, the comparative efficacy of different NIBS techniques remains unclear. Therefore, this network meta-analysis (NMA) compared the effects of NIBS interventions on pain intensity, anxiety, and depressive symptoms in CMP.
MethodsWe searched seven databases from inception to 7 October 2025, including PubMed, the Cochrane Library, Web of Science, Embase, MEDLINE, PsycINFO, and CINAHL, and included only English-language randomized controlled trials evaluating NIBS for CMP that reported pain, anxiety, or depression outcomes. Effect sizes were synthesized using a frequentist NMA and expressed as standardized mean differences (SMDs) or mean differences (MDs) with 95% confidence intervals (CIs). Risk of bias was assessed with the Cochrane Risk of Bias 2.0 tool.
ResultsA total of 50 randomized controlled trials were included, involving 2,203 participants with an average age ranging from 31 to 75 years; approximately 82% of the participants were women. The NMA showed that: (1) in the overall CMP population, low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (SMD = − 1.19, 95% CI − 1.86 to − 0.52), transcranial random noise stimulation (tRNS) targeting the primary motor cortex (M1) (SMD = − 1.66, 95% CI − 3.05 to − 0.28), and intermittent theta-burst stimulation (iTBS) targeting the DLPFC (SMD = − 0.78, 95% CI − 1.63 to 0.08) ranked first for pain, anxiety, and depression, respectively. Sensitivity analyses suggested that LF-rTMS targeting the DLPFC may be the most robust option for CMP with comorbid emotional symptoms; (2) in fibromyalgia, LF-rTMS targeting the DLPFC ranked first for pain (SMD = − 1.19, 95% CI − 1.99 to − 0.39) and depression (SMD = − 0.63, 95% CI − 0.98 to − 0.27), while tRNS targeting M1 (SMD = − 1.66, 95% CI − 2.99 to − 0.34) ranked first for anxiety; after excluding sparse-evidence interventions, transcranial direct current stimulation (tDCS) targeting M1 became the preferred option for anxiety; (3)in non-fibromyalgia populations, cranial electrotherapy stimulation (CES) (SMD = − 1.39, 95% CI − 2.41 to − 0.37) ranked first for pain, while iTBS targeting the DLPFC (MD = − 0.79, 95% CI − 1.48 to − 0.10) showed potential benefit for depression, although supporting evidence was limited.
ConclusionsDifferent non-invasive brain stimulation modalities may confer outcome-specific benefits in chronic musculoskeletal pain. Overall, low-frequency repetitive transcranial magnetic stimulation targeting the dorsolateral prefrontal cortex showed relatively robust effects across outcomes in chronic musculoskeletal pain and on pain and depression in fibromyalgia; however, further high-quality clinical trials are needed.
PROSPERO registrationCRD420251131206.