Efficacy and Safety of Non-invasive Brain Stimulation in Non-migraine Primary Headache Disorders: A Systematic Review and Meta-analysis.

BACKGROUND AND

OBJECTIVES

Non-migraine primary headache disorders such as tension-type headache and cluster headache are often chronic and significantly impair quality of life, with limited effective treatment options. Non-invasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), have emerged as promising neuromodulatory therapies. This systematic review evaluated the effectiveness and safety of NIBS in reducing headache frequency and intensity in non-migraine primary headache disorders.

METHODS

This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A systematic search of PubMed, Embase, Scopus, and Google Scholar was conducted up to February 25, 2025. Randomized controlled trials and non-randomized studies assessing NIBS modalities in non-migraine primary headache disorders were included. Primary outcomes were headache frequency, intensity, and adverse effects. Meta-analysis was performed using a random-effects model, with subgroup analyses and heterogeneity assessed using the I 2 statistic. This review was registered with PROSPERO (CRD420250651461).

RESULTS

Of 1,043 records screened, 14 studies ( N = 690) met the inclusion criteria, of which 9 were eligible for meta-analysis. NIBS significantly reduced headache severity [standardized mean difference (SMD) = -1.30; 95% confidence interval (CI): -2.03 to -0.57; P = 0.0005] and disability (SMD = -1.49; 95% CI: -2.41 to -0.57; P = 0.001). Subgroup analysis showed greater efficacy of rTMS compared with tES. Reduction in headache frequency was not statistically significant. Adverse events were mild and infrequent. Most studies had a moderate to high risk of bias.

CONCLUSIONS

NIBS, particularly rTMS, may be effective in reducing headache severity and disability in non-migraine primary headache disorders. However, further high-quality, large-scale studies are needed to establish its role in routine clinical practice.