Prednisone demonstrates efficacy as preventive treatment for episodic cluster headache

Oral prednisone led to a greater decrease in the number of episodic cluster headaches within the first week of treatment vs. placebo, according to findings from a multicenter trial published in The Lancet Neurology.

“Corticosteroid treatment in cluster headaches is widely used in clinical practice, but the absence of a standardized dosage regimen, continued discussion about its uncertain clinical benefits and potential side effects result in limited use by pain specialists, general neurologists and affected patients,” the researchers wrote. “The concern about side-effects is not generally based on realistic probability, but often confuses transient and infrequent short-term effects (eg, glaucoma, increased blood pressure, fluid retention, mood swings, etc) and common long-term side-effects (eg, suppressed adrenal gland hormone production or osteoporosis).”

Several “carefully described studies and case series” that examined the effectiveness of corticosteroids for cluster headache have been completed in the past 40 years, according to the researchers, but these investigations “do not completely satisfy modern standards in terms of randomization procedures, blinding of participants and data analysis.”

As a result, Mark Obermann, MD, of the Center for Neurology at Asklepios Hospitals Schildautal and the department of neurology at University Hospital Essen, both in Germany, and colleagues conducted the prednisone in cluster headache (PredCH) trial to evaluate the safety and effectiveness of 100 mg oral prednisone daily for the short-term prevention of episodic cluster headaches.

The multicenter, randomized, double-blind, placebo-controlled trial at 10 headache centers in Germany included patients with episodic cluster headaches aged 18 to 65 years who were within a current pain episode for no more than 30 days. Obermann and colleagues enrolled 116 patients in the study between April 2013 and January 2018.

The researchers randomly assigned participants to prednisone 100 mg for five days (n = 57) or placebo (n = 59). Prednisone administration was followed by a tapering of 20 mg every 3 days. All patients received oral verapamil for long-term prevention, with an initial 40 mg dose three times per day that increased to 120 mg three times per day for the remainder of the study. The modified intention-to-treat analysis included 109 patients (prednisone, n = 53; placebo, n = 56).

Participants in the prednisone group experienced a mean number of 7.1 episodic cluster headache attacks within the first week of treatment compared with 9.5 attacks in the placebo group (difference, –2.4 attacks; 95% CI, –4.8 to –0.03), according to the researchers. As a result, the mean number of cluster headache attacks in the first week was 25% less in the prednisone group compared with the placebo group.

“The assessment showed similar results in favor of prednisone treatment compared with placebo of mean attacks of 7.1 (standard deviation [SD], 6.5) vs. 9.8 (SD, 6.2) for best observation carried forward (difference, –2.7; 95% CI, –5.1 to –0.3), and mean attacks of 7.4 (SD, 6.4) vs. 10.6 (SD, 7.6) for worst observation carried forward (difference, –3.2; 95% CI, –5.9 to –0.5,” Obermann and colleagues wrote.

After 7 days, the number of days with cluster attacks was 3.9 (SD, 2.4) with prednisone vs. 5.1 (SD, 1.8) with placebo (difference, –1.2; 95% CI, –2 to –0.3). At day 28, the number of days with cluster headache attacks was 8.8 (SD, 7.1) for the prednisone group vs. 11.9 (SD, 7.1) for the placebo group (difference, –3.2; 95% CI, –6.9 to 0.5).

The researchers found that more patients who received prednisone reported a decrease in cluster headache attack frequency of at least 50% at day 7 compared with placebo (49% vs. 15%). The number of participants with at least a 50% decrease in attack frequency increased to 71% of patients receiving prednisone compared with 45% of patients receiving placebo at day 28.

Obermann and colleagues reported 270 adverse events. In the prednisone group, 71% of patients experienced adverse events; the most common events included headache, palpitations, dizziness and nausea. In the placebo group, 71% of patients experienced adverse events, with nausea, dizziness and headache occurring most often.

“Oral application of prednisone ... is an effective and fast-acting, short-term preventive treatment for episodic cluster headache that can be used to attenuate the early cluster episode until long-term prevention has reached its full efficacy. Patients without concurrent health issues could be considered for prednisone treatment alongside the initiation of verapamil for long-term prevention,” the researchers wrote. “The best combination of prednisone with long-term preventive medication should be investigated in future studies.”