Efficacy, IHS Guideline Adherence, and Methodological Quality of Noninvasive Neuromodulation Clinical Trials in Migraine and Cluster Headache: A Systematic Review.

BACKGROUND

Noninvasive neuromodulation has emerged as a promising approach for acute and preventive treatment of migraine and cluster headache. This systematic review evaluates how noninvasive neuromodulation trials align with guidelines by the International Headache Society (IHS), their efficacy on IHS-recommended outcomes, and the robustness of the supporting evidence.

METHODS

A systematic search of MEDLINE, Embase, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform was conducted for clinical trials published between January 1990 and October 2024. Studies evaluating noninvasive neuromodulation for acute or preventive treatment of migraine or cluster headache were included based on predefined eligibility criteria. Data were analyzed with respect to study design, adherence to endpoints recommended by IHS, and efficacy of reported outcomes.

RESULTS

Seventy trials met inclusion criteria, covering modalities such as noninvasive vagus nerve stimulation (nVNS), external trigeminal nerve stimulation (e-TNS), single- and repetitive transcranial magnetic stimulation (sTMS, rTMS), and remote electrical neuromodulation (REN), among others. For migraine, acute treatment studies were mostly randomized, sham-controlled, and blinded, while preventive trials showed greater variability. Significant heterogeneity was noted in the use of IHS-recommended endpoints. For cluster headache, nVNS remains the only modality evaluated.

CONCLUSIONS

Noninvasive neuromodulation holds potential for acute and preventive treatment of migraine and cluster headache. However, considerable variability exists in study design, outcomes, and adherence to IHS guidelines across trials. Additional robust, sham-controlled studies are needed to validate the clinical efficacy of these interventions.