Greater occipital nerve injection with methylprednisolone as transitional therapy in episodic cluster headache: Results from an RCT

Objective We investigated whether greater occipital nerve injection (GON injection) with 80 mg of methylprednisolone at the onset of a cluster headache episode would reduce attack frequency faster than standard therapy with verapamil alone, and reduce the need for verapamil and the risk of adverse events (AEs). Methods This was an investigator-initiated, randomised, double-blind, 12-week clinical trial. Participants received GON injection with 80 mg of methylprednisolone (n = 36) or placebo (n = 34) within two weeks (median) after the onset of a cluster episode, followed by standard verapamil therapy and e-diary monitoring. The primary endpoint was the mean daily dose of verapamil over the entire 12-week study period. Key secondary endpoints were reduction in the mean daily dose of verapamil over the first four weeks and attack frequency reduction in the first week. Results In the verum vs. placebo group, the mean daily dose of verapamil during the total 12-week study period did not differ (232 ± 188 mg vs. 244 ± 143 mg; Δ = 12 mg, 95% confidence interval (CI) = −68 to 92; p = 0.230). However, exploratory analysis of the secondary endpoints showed a lower verapamil dose in the first four weeks in the methylprednisolone group compared to placebo (227 ± 126 mg vs. 287 ± 107 mg; mean Δ 60 mg; 95% CI = −4 to −116), as was the median number of attacks at week 1 (7 (interquartile range = 2–11.75) vs. 10 (interquartile range = 6–17.5); 95% CI = −1.0 to −8.0), the mean attack intensity at week 1 (5.7 ± 1.9 vs. 6.6 ± 1.8; 95% CI = 0.0–1.8) and throughout the 12-week study period (5.0 ± 1.8 vs. 5.9 ± 1.9; 95% CI = 0.01–1.8), and the number of days with adverse events (455/2520 (18%) vs. 605/2850 (21%); p < 0.01). There were no serious AEs. Comclusions This study failed to establish its primary endpoint. However, exploratory analysis of the secondary endpoints revealed that GON injection with 80 mg of methylprednisolone at the beginning of a cluster headache episode followed by standard therapy verapamil is a safe transitional treatment that provides faster reduction in attack frequency and intensity than verapamil alone, decreases the mean verapamil dose over the first four weeks with consequently fewer adverse events in the first four weeks after the injection. Trial Registration This study is registered on Clinicaltrials.gov with registration number NCT04014634 at 08-07–2019. First inclusion was on 30-07-2019.