Prednisone Reduces Cluster Headache Attacks During Verapamil Titration

Transitional treatment with tapered doses of oral prednisone reduced cluster headache attacks while verapamil was being started for long-term cluster headache prevention, a randomized controlled trial found.

“Oral prednisone was an effective short-term preventive therapy in our population of patients with episodic cluster headache,” wrote Mark Obermann, MD, of Asklepios Hospitals Schildautal in Germany, and co-authors in Lancet Neurology.

“Our findings support the use of prednisone as a first-line treatment in parallel to the up-titration of verapamil, although the efficacy of prednisone alongside other long-term prevention requires additional investigation,” they added. “Comparison of oral corticosteroid treatment with greater occipital nerve injection is warranted to determine the future best medical practice, as occipital nerve injection is a more invasive approach than oral prednisone, but it does provide less systemic corticoid exposure.”

The trial, which was stopped early due to slow recruitment and expired funding, enrolled adults with episodic cluster headaches in a current pain episode for not more than 30 days between April 2013 and January 2018. Participants were randomized to short-course oral prednisone (100 mg oral prednisone for 5 days followed by tapering of 20 mg every 3 days; n=53) or placebo (n=56).

All patients received oral verapamil for long-term prevention (40 mg three times daily increased to target dose of 120 mg three times daily by day 19). Followup was at 7 and 28 days.

Over the first 7 days, patients treated with steroids compared to placebo had:

• Fewer number of attacks, 7.1 versus 9.5, P=0.002.
• Fewer number of days with cluster attacks, 3.9 versus 5.1, P=0.0141.
• Less need for acute treatment, mean doses 9.2 versus 6.0, P=0.0012.
• Greater rate of complete cessation of attacks, 35% versus 7%, P=0.0006.
• Higher proportion of patients who experienced at least 50% reduction in attacks, 49% versus 15%, P=0.0001.

By day 28, the number of attacks remained fewer and the proportion of patients with at least 50% reduction in attack frequency was greater in the prednisone group.

“Obermann and colleagues have provided the first large and robust controlled trial showing the efficacy of oral steroids for short-term transitional treatment of cluster headache,” noted Anne Ducros, MD, PhD, of the University of Montpellier in France, in an accompanying editorial. “Research on cluster headache is scarce and poorly funded as compared with research into other neurological disorders that have a similar heavy burden.

Cluster headache manifests as short, unilateral headaches (15-180 minutes; up to 8 times daily) with ipsilateral autonomic symptoms (conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis and/or eyelid edema) and/or agitation. It affects about 1 in 1000 people.

Treatment involves acute symptom control and initiation of a long-term prophylactic, with or without transitional therapy during titration of the prophylactic. Prophylaxis is typically with verapamil; lithium has also been used and galcanezumab has recently been studied as well, with once monthly subcutaneous dosing reducing attack frequency compared with placebo.

Transitional therapy with suboccipital steroid injections was effective in reducing the number of daily attacks in a 2011 study. A 1975 report that 17 of 19 patients treated with oral prednisone benefitted after not responding to standard treatment of the day (methysergide, caffeine, ergotamine preparation, phenobarbital, and analgesics) occurred early in decades-long use of oral steroids for transitional treatment. However, this strategy has not been tested in large randomized trials, the researchers noted.

In their study, Obermann and colleagues recruited adult patients with active cluster headache from 10 German specialized pain and headache centers. Patients were not taking any prophylactic medication. They excluded people with diabetes, cardiac arrhythmia, arterial hypotension or hypertension, gastrointestinal ulceration, severe osteoporosis, glaucoma, tuberculosis, current infection, poliomyelitis, lymphadenitis, and chronic cluster headache.

Mean age was 42.4 for the prednisone and 40.3 for the placebo group. Females made up 16% to 17% of both groups. Prior treatment with verapamil was noted for 98% of the prednisone group and 97% of the placebo group.

The primary endpoint was the mean number of attacks within the first week of treatment with prednisone compared with placebo, where attack was defined as a unilateral headache with moderate-to-severe intensity of at least 5 on a numerical rating scale of 0-10.

Two serious adverse events, inguinal hernia and severe deterioration of cluster headache, were reported, both in the placebo group. Among the most common events in prednisone and placebo groups were headache, dizziness, and nausea. Palpitations were also common in the prednisone group.

Ongoing concerns about using oral steroids include possible severe systemic toxic effects with intermittent long-term use, resistance, and the potential for misuse, Ducros noted.

Deciding when oral steroids are appropriate as transitional therapy should include comparison to greater occipital nerve injections and comparisons of various acute, transitional, and preventive therapies, she suggested. Determining the best verapamil regimen in the setting of multiple titration schedules and target doses may be of particular importance: “With higher doses and more rapid escalation of verapamil, transitional treatment with steroids might be reserved for patients with resistant bouts and more than two attacks per day.”

Limitations included difficult recruitment and an underpowered study. “Patients with good experience with corticosteroids in previous cluster episodes were hesitant to participate in this trial as they were concerned about being randomly assigned to the placebo group,” the researchers noted. Experience with corticosteroids also may have unblinded some participants.

1. Transitional treatment with tapered doses of oral prednisone reduced cluster headache attacks while verapamil was being started for long-term cluster headache prevention, a randomized controlled trial found.

2. Over the first 7 days after starting treatment, patients treated with prednisone compared with placebo had a fewer number of attacks, fewer number of days with cluster attack, less need for acute treatment, greater rate of complete cessation of attacks, and a higher proportion of patients with at least 50% reduction in attack frequency.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Cat ID: 130

Topic ID: 82,130,130,35,192,925