Perimenstrual repetitive greater occipital nerve blockade for menstrual migraine: a randomized, double-blind, placebo-controlled trial

Abstract Background The main purpose of this study is to demonstrate the decrease in headache severity, pain duration and the number of painful days in a month after repetitive GON blockade applied with local anesthetic in menstrual migraine patients compared to the placebo group. Methods This randomized, double-blind, placebo-controlled study included 48 menstrual migraine patients. 24 patients received medication (0.5% bupivacaine) and 24 received placebo (saline) GON blockade twice a month for three months. Baseline data (month 0) relied on retrospective recall, whereas post-treatment data (months 3 and 6) were collected prospectively using a paper-based headache diary. The primary outcome was the change in headache severity (VAS score). Secondary outcomes included attack frequency, duration, number of headache days, analgesic use, and MIDAS scores. Results Baseline characteristics were similar between groups. At month 3, the active group showed a significantly greater reduction in the primary outcome, VAS scores, compared to the placebo group (decreasing from 8.75 ± 0.67 to 3.80 ± 3.18 vs. 8.71 ± 1.04 to 7.16 ± 1.31; p < 0.001). Significant reductions were also observed in secondary outcomes including monthly attack frequency ( p = 0.002), mean attack duration ( p < 0.001), number of headache days ( p = 0.002), MIDAS scores ( p = 0.003), and analgesic use ( p = 0.009). Mild, transient injection-site tenderness was the only reported side effect. The clinical improvements were maintained at the 6th month, suggesting a potential sustained benefit, though natural history or late placebo responses cannot be fully excluded. Conclusion Repetitive perimenstrual GON blockade may be an effective short-term prophylaxis for MM. However, the observed effects on the subjective primary endpoint (VAS) may be partially attributable to imperfect blinding, and all secondary outcomes are exploratory. Further studies are needed to confirm these findings and exclude natural history or placebo responses. Trial registration ClinicalTrials.gov, NCT07576309. Registered on 08 May 2026. Retrospectively registered.