To investigate the efficacy of oral prednisone in patients with episodic cluster headache (CH) in a multicenter, randomized, double-blind, placebo-controlled trial.

Prednisone is commonly used for initial short-term therapy to close the gap between the first attacks and the onset of preventive medication such as verapamil. However, this therapeutic approach was never investigated in a prospective randomized controlled trial.

Patients received 100 mg oral prednisone for five days then tapered by 20 mg every three days or placebo in parallel to an increasing dose of verapamil starting with 40 mg three times per day. The primary endpoint was the mean number of cluster headache attacks within the first week during treatment with prednisone compared to placebo. Key secondary endpoints were reduction of attacks by more than 50% at day seven compared to baseline as well as number of patients with complete cessation of cluster headache attacks. Quality of life, depression and safety were also assessed.

In total, 118 patients between 18 to 65 years were enrolled in the study and 109 were included in the intention-to-treat (ITT) analysis. 53 patients received prednisone and 56 placebo. The mean number of CH attacks in the prednisone group during the first week was 7.1 attacks (SD: 6.5, 95%CI 5.3 8.9) compared to 9.5 attacks with placebo (SD: 6.0, 95%CI 7.9 11.2], p=0.02). 17 patients in the prednisone group (34.7%) reported complete cessation of CH attacks after one week compared to only four patients (7.4%) in the placebo group. Attack reduction of at least 50% was reported by 25 (49%) patients receiving prednisone compared to 8 (14.5%) placebo (p<0.01). No relevant side effects were observed.

Oral prednisone was superior to placebo in reducing the frequency of attacks and should be used to attenuate the early CH episode until long-term prevention becomes effective.