Short-term gepant use during active cluster headache bouts: A consecutive case series

AimTo evaluate the short-term effectiveness and tolerability of gepants administered during active cluster headache (CH) bouts in routine clinical practice, focusing primarily on reduction in daily attack frequency and additionally on pain intensity, bout duration, and patient-reported outcomes.MethodsWe conducted an observational, uncontrolled, consecutive case series at a reference headache clinic. Patients fulfilling ICHD-3 criteria for episodic or chronic CH who initiated a standardized 28-day course of a gepant during an active bout between October 2024 and July 2025 were included. Baseline data were abstracted from clinical records and diaries. No systemic corticosteroids, greater occipital nerve blocks, preventive dose adjustments, or new preventives were introduced during the 28-day period. The primary endpoint was ≥50% reduction in mean daily attack frequency at the end of treatment compared with baseline. Secondary outcomes included change in pain intensity (Numerical Rating Scale, NRS), change in attack duration, impact on overall bout duration, Patient Global Impression of Change (PGIC), and adverse events. Analyses were descriptive.ResultsTen patients were included (seven episodic CH [ECH], three chronic CH [CCH]). Median baseline attack frequency was three attacks/day (range 1-6), and median baseline NRS was 8.5. The primary endpoint was achieved in 7/10 patients (70.0%): 5/7 with ECH (71.4%) and 2/3 with CCH (66.7%). Two ECH patients with a low baseline frequency (two attacks/day) did not meet the ≥50% criterion but demonstrated marked reductions in pain intensity and shortened bout duration. Overall, pain intensity improved in 9/10 patients (90.0%), with a median NRS reduction of 7 points (range 0-10). Median intensity reduction was greater in ECH (7 points; range 2-10) than in CCH (2.5 points; range 0-5). Shortening of individual attacks was reported in 4/10 (40.0%), and reduction in overall bout duration in 7/10 (70.0%), predominantly among ECH. Median time to perceived benefit was 96 h. Adverse events were mild (nausea or constipation in 2/10).ConclusionIn this small real-world case series, short-term gepant use during active cluster bouts was associated with multidimensional clinical improvement, particularly in episodic CH. Benefits extended beyond attack frequency to include substantial reductions in pain intensity and apparent modulation of bout duration. Given the uncontrolled design and limited sample size, findings should be interpreted cautiously but support further prospective, phenotype-stratified investigation.