Oral steroid effectively mutes cluster headache attacks

Oral prednisone was effective in reducing the frequency of episodic cluster headache attacks in the short term, according to the PredCH* study. 

While preventive therapy such as verapamil has been shown to be effective, it has a delayed onset of action of 10–14 days. Therefore, international guidelines recommend initiating corticosteroids as short-term preventive treatment while waiting for long-term preventive drugs to take effect.

“[However,] treatment recommendations have been based mainly on expert opinion and specialists’ treatment habits,” the researchers noted. “[Also,] the absence of a standardized dosage regimen, continued discussion about its uncertain clinical benefits, and potential side effects result in limited use.”

“[This study] now provides strong and long-awaited evidence supporting the use of oral steroids as a transitional treatment option,” wrote Dr Anne Ducros from the University of Montpelier, France, in an accompanying commentary. [Lancet Neurol 2020;doi:10.1016/S1474-4422(20)30402-6]

In the double-blind multicentre trial, 116 patients with episodic cluster headaches were randomized 1:1 to receive oral prednisone or a matching placebo. Prednisone was initially given at 100 mg for the first 5 days, and tapering by 20 mg every 3 days thereafter (total exposure of 17 days). All patients were also treated with oral verapamil for long-term prevention, starting from 40 mg, which was then titrated up to 120 mg thrice daily. [Lancet Neurol 2020;doi:10.1016/S1474-4422(20)30363-X]

Within the first week of treatment, the prednisone group had significantly reduced cluster headache attacks than the placebo group (mean, 7.1 vs 9.5 episodes; p=0.002).

Moreover, cluster headache attacks had completely stopped within the first week in 35 percent of patients treated with prednisone compared with 7 percent in the placebo group (p=0.0006).

There were also significantly more prednisone-treated patients who reported ≥50 percent reduction in attack frequency compared with the placebo group within the first week (49 percent vs 15 percent; p=0.0001), which was sustained through 28 days (71 percent vs 45 percent; p=0.011).

In terms of safety, adverse events (AEs) occurred at similar rates in both treatment groups, at 71 percent each, with nausea, dizziness, and headache being the most common. Two serious AEs were reported — inguinal hernia and severe worsening of cluster headache — both of which occurred in the placebo group.        

“Our findings suggest that patients with episodic cluster headache without any concurrent health issues could receive prednisone treatment for each new cluster headache episode along with the initiation of preventive treatment for the longer term,” said the researchers.

 Important step forward

Compared with previous randomized trials which have shown the efficacy of suboccipital steroid injections as transitional therapy for cluster headache, the oral protocol in the current study provides a more convenient option, Ducros pointed out.

Meanwhile, the current study also raises more questions for further research, such as the optimum dose of oral steroids required to relieve a bout of headache attack, comparative efficacy vs occipital steroid injections, the optimum verapamil regimen to be used in combination, and risk of long-term cortico-resistance.

“Despite these outstanding issues, the results of the study … provide an important step forward for patients with cluster headache, for whom safe and effective transitional therapies are much needed,” she commented.

“Future research should investigate which long-term preventive medications prednisone could be combined with for maximum benefit,” the researchers suggested.

*PredCH: Prednisone in cluster headache