Neuromodulation in the Management of Cluster Headaches: a Systematic Review and Meta-Analysis

Background: Cluster headache is one of the primary types of headaches that is characterized by unilateral excessive pain that is mostly associated with autonomic symptoms. The management of cluster headache usually consists of high flow oxygen, triptans, and verapamil. The exploration of new methods, such as neuromodulation techniques are needed to look for possible alternatives for patients that remain refractory to all types of medications. Methods: Databases including Pubmed, Cochrane, Web of Science, and Google Scholar were systematically reviewed through 2025 for studies involving adult patients (≥18 years) with cluster headache. The terms used for the search included (e.g., occipital nerve stimulation, vagus nerve stimulation, transcranial magnetic stimulation, sphenopalatine ganglion stimulation). The aim was to measure the outcomes of neuromodulation in reducing headache frequency and pain intensity, improving quality of life, and assessing adverse effects. Results: Ten studies met the inclusion criteria. Meta-analysis showed no statistically significant difference in attack frequency (SMD: –0.05; 95% CI: –0.36 to 0.26; p = 0.75) or pain intensity (SMD: –0.26; 95% CI: –0.57 to 0.05; p = 0.10) between neuromodulation and control groups. However, neuromodulation was associated with a significant outcome in improving quality of life (SMD: –0.50; 95% CI: –0.82 to –0.19; p = 0.002). The overall risk of adverse events was comparable between groups (OR: 1.38; 95% CI: 0.37–5.08; p = 0.63), though, the heterogeneity was high in the studies Conclusion: Neuromodulation has been shown to improve the quality of life, specifically to the patients who are refractory to standard management of cluster headache, but it does not reduce the attack frequency or pain intensity. These modalities are generally safe, according to the evaluated high quality randomized trials.