Serial suboccipital injections of steroids rapidly relieve cluster headaches as a transitional treatment while patients wait for long-term prophylactic drugs to take effect, according to a randomized, double-blind, controlled clinical trial.
Compared with placebo injections, cortivazol injections reduced the number of headaches per day during the first 4 days of treatment, decreased the total number of attacks over 15 days while patients waited for verapamil to kick in, and shortened the interval until remission, reported Dr. Elizabeth Leroux of the Emergency Headache Centre, Lariboisière Hospital, Paris, and her associates.
Cluster headache is characterized by attacks of strong periorbital pain with ipsilateral autonomic signs, which recur up to eight times a day. Episodic cluster headaches occur in phases for weeks or months separated by long remissions. Ina10% of patients, episodic cluster headaches evolve into chronic cluster headaches.
Most patients are managed with a combination of acute therapy and prophylactic treatment. Transitional treatment is used to suppress attacks at the onset of a cluster while awaiting the delayed efficacy of preventive drugs such as verapamil or lithium. Oral steroids are widely used in this setting, but they can induce rebound attacks when patients are weaned off them and can cause serious adverse effects even when used briefly.
Suboccipital steroid injections have been proposed as an alternative to systemic steroids, but only one small, randomized, controlled trial on this approach has been published. Dr. Leroux and her colleagues, who have used suboccipital cortivazol injections for 10 years in their clinic, assessed their safety and efficacy when added to usual care. (Cortivazol is not available in the United States.)
During an 8-month period, the investigators enrolled 43 adults who presented to the Emergency Headache Center with frequent daily cluster headaches, including 28 with episodic and 15 with chronic cluster headache. The study subjects were randomly assigned to receive three suboccipital injections containing either cortivazol (21 patients) or saline (22 patients), given singly every 48–72 hours.
The injections were made under the occipital bone at the medial third between the inion and mastoid process, ipsilateral to the attack. Each injection was aimed in three directions: upward, at a 45-degree angle to the left, and at a 45-degree angle to the right.
Acute treatment with sumatriptan or oxygen was given as needed. Patients continued on any prophylactic agents they had been taking before the attack or were started on verapamil.
The study subjects completed daily diaries in which they recorded cluster headache attacks, medication use, and adverse effects for 90 days. All were telephoned after 3-11 months to assess their satisfaction with treatment.
The study's primary end point was to reduce the mean number of daily attacks to two or fewer on the second, third, and fourth days after the final injection. In all, 20 of 21 patients (95%) who received steroid injections reached this end point, compared with 12 of 22 controls (55%) who received placebo injections.
This significant benefit with active injections was the same for both episodic and chronic cluster headaches, reported the investigators (Lancet 2011 Sept. 7 [doi:10.1016/S1474-4422(11)70186-7]).
Patients given steroid injections also had fewer attacks during the first 15 days of the study than did those given placebo, and achieved remission a mean of 7 days earlier. Cortivazol also lowered the need for sumatriptan injections during the first 15 days of the study and reduced the need for verapamil in patients with the episodic type of cluster headache.
In addition, patients' scores of satisfaction with therapy were higher for steroid than for placebo injections.
In a post hoc analysis, 7 of 21 patients (33%) given cortivazol remained pain free from 4 days after the first injection until day 30, while only 2 of 22 control subjects (9%) did. Eleven (52%) in the cortivazol group remained pain free after the last injection to day 30, compared with only 4 (18%) in the control group.
The injections were safe and well tolerated. Adverse events – chiefly neck pain at the injection site and headache other than cluster headache – developed in 18 (86%) of the cortivazol group and 14 (64%) of the control group.
This study received no industry funding. Dr. Leroux and her associates reported ties to numerous industry sources, including Sanofi-Aventis, maker of the prefilled cortivazol syringes used in this study.
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Robust, Long-Awaited Data
The study by Dr. Leroux and her colleagues provides “long-awaited evidence in support of” suboccipital steroid injections for cluster headache, said Dr. David W. Dodick.
“Leroux and colleagues have provided the clinical and academic community with the largest and most robust controlled trial to date showing efficacy of suboccipital steroid injections for short-term transitional treatment of cluster headache,” he said.