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Botulinum Toxin for Cluster Headache; 10 Patients
Posted August 2001

Ten chronic cluster headache patients received botulinum toxin for refractory clusters.

The injections were done with low dose botulinum toxin; either 24 units of BTA per patient, or the equivalent BTB (1200 units). These were patients who had been refractory to the usual preventive and abortive medications for cluster headache. Side effects were minimal in this study. For the 7 chronic cluster patients, the injections were moderately effective in 3/7, and extremely effective for one. The botulinum toxin was not effective for 3 of the chronic cluster sufferers. Of the 3 episodic cluster sufferers, 1 obtained complete relief and 1 had moderate relief. The 3rd achieved complete relief with the first set of injections, but only moderate improvement after a further set of injections one year later.

Most patients with cluster headache receive some degree of relief from the usual preventive medications. These include verapamil, lithium, cortisone, sodium valproate, indomethacin, etc. In addition, many of the patients obtain relief from the abortive medications. The abortives include oxygen, sumatriptan injections, sumatriptan nasal spray, other forms of triptans, lidocaine nasal spray, etc. Many patients with cluster headache do not achieve an adequate response to the preventive or abortive medications. Botulinum toxin has shown promise in the treatment of migraine headache. Many therapies that have been useful for migraine headache also are somewhat beneficial for cluster headache. This study evaluated 10 patients with refractory cluster headache who were given botulinum toxin type A (BTA) or botulinum toxin type B (BTB) injections.

There were 8 male patients and 2 females, ages 28 to 63, in this study. Seven patients had chronic cluster headache, and three suffered from episodic clusters. They were refractory to the usual preventive medications. Each patient kept a headache diary, using a visual analog scale, for four months post-injection. Twelve injections of 2 units of BTA (or 100 units of BTB) were utilized. Thus, the total was 24 units BTA, or 1200 units of BTB, per patient, which is a low dose.Eight injections were given frontally and temporally ipsilateral to the pain, and four in the contralateral frontal area. The case summaries are as follows:

Chronic Cluster Patients (7): (1). 59 year old man with chronic clusters, in a severe exacerbation (2 to 3 per day). BTA was not effective. (2). 63 year old man with chronic clusters, in a severe exacerbation (4 to 5 per day). BTA was moderately effective.The clusters decreased to one daily. This relief lasted 4 months.He had been scheduled to have a surgical procedure for the clusters, but cancelled it due to the relief from the BTA. (3). 53 year old man with chronic clusters, in a moderate exacerbation. No relief from the BTA. (4). 38 year old man with chronic clusters in a severe exacerbation.There was dramatic, immediate relief after the BTA injections, with no headache for 3 months. (5). 28 year old man with chronic clusters. BTB was moderately effective. The clusters decreased from 4 to 5 per day down to 1 daily. The relief lasted 2 months. (6). 48 year old man with 2 cluster headaches per day. BTB was moderately effective.Clusters decreased to 0 to 1 attack per day, and this relief lasted 2½ months. (7). 52 year old female with chronic clusters; BTB was not effective.

Episodic Cluster Patients (3): (1). 62 year old man with episodic clusters, 2 per day. Complete relief after BTA (the injections immediately stopped the cycle). (2). 43 year old man with severe episodic clusters. He received 2 sets of injections, one year apart. After the first BTA injections there was immediate, complete relief. The second time, with BTB, there was only moderate improvement. After the second set, the clusters diminished from 4 per day (lasting 1 to 2 hours each) down to 1 headache daily lasting less than 1 hour. (3). 47 year old female with episodic cluster headache. The attacks occurred 3 times daily, and she had moderate relief after the BTB. The attacks decreased to 0 or 1 per day. The relief lasted for the remainder of the cycle.

One patient experienced a mild ptosis for 12 days post-injection. One patient described a burning sensation in both eyes that resolved after 6 days.

There were 7 chronic cluster headache patients.Botulinum toxin was ineffective for 3 of the patients. The injections were moderately effective for 3 of the cluster sufferers.One patient had dramatic, immediate relief that lasted for 3 months. There were 3 episodic cluster headache patients.One had complete relief, one experienced moderate relief, and the third achieved complete relief with his first set of injections, but only moderate improvement one year later, after the second set of injections.


Botulinum toxin is a safe therapy that, although expensive, is relatively easy to administer. This small study demonstrated that, for some refractory cluster patients, botulinum toxin may be a worthwhile treatment. It is possible that larger doses (low doses were utilized in this study) would be more effective.

There have been a number of studies of botulinum toxin (primarily BTA, Botox) for the treatment of migraine and tension headache. The initial retrospective chart review of 106 patients revealed that 46% achieved complete relief from their migraines. Another 30% had partial improvement. The mean dose in this study was 35.5 units of BTA per patient. There have been several positive prospective randomized trials in migraineurs since that time. In one of the key studies, both the 25 unit (total) BTA patients and the 75 unit patients did better than the patients who received placebo. However, the patients who had received 75 units did have significantly more treatment-related adverse advents (primarily forehead weakness) than placebo. In another study, 51% of patients had complete relief for a mean of 4.1 months, and 38% reported a partial response. This was an open label trial of 77 patients with migraine headache.

Another open-label study over a three year period did include a small number of cluster headache patients. The doses were higher in this study, 80-150 units of BTA. Fifty-eight percent of patients with chronic tension-type headache achieved positive outcomes, 67% of migraine sufferers responded favorably, and 2 of the 4 patients with cluster headache had positive responses. In these cluster patients, a positive response was determined by termination of the cluster episode within 3 weeks of BTA injections. These same investigators went on to conduct a double blind, placebo controlled, randomized study involving 40 patients with chronic tension-type headache. The number of headache-free days was significantly increased in the BTA group at 3 months post treatment. Other studies have not been as positive for tension-type headache, however. One study that was double blind, placebo controlled and randomized revealed no significant differences through 12 weeks for chronic tension-type headache. One further report on 2 patients with episodic cluster headaches revealed complete relief after 50 units of BTA. These injections were given ipsilateral to the pain.

Naturally, in the beginning years of treatment utilizing botulinum toxin for cluster headache, only the more refractory patients will be injected. However, if experience and studies dictate that botulinum toxin is an effective therapy, and with some reduction in cost, this may become a standard treatment. The question as to the dose of injection has not been adequately answered in the studies. There are studies that indicate that low doses may be as effective as high doses. Higher doses carry the risk of increased adverse events. Further studies will be needed to determine the adequate dose. As to the location of the injections, it makes sense intuitively to inject primarily on the ipsilateral side of the cluster headache. However, a number of studies will be needed to determine the most effective location for botulinum toxin injections.

There are relatively few disadvantages for the utilization of botulinum toxin for cluster headache. Cost, pain during the injections, and the possibility of ptosis are some of the considerations.

Botulinum toxin is a relatively safe treatment, particularly in the low doses that have been utilized for migraine headache. If adequate efficacy for cluster headache can be established, botulinum toxin may become a primary first line therapy for the treatment of cluster headache.