SAN FRANCISCO—Botulinum toxin type A, more commonly known as Botox, may safely and effectively reduce the impact and disability of migraine, said Curtis P. Schreiber, MD. Botulinum toxin treatment did not reduce the number of headaches that a patient developed, but it did reduce headache severity, according to results from a randomized trial.

“The patients overall reported the same number of headaches,” said Dr. Schreiber. “But at the end of eight months, there was a significant drop, at least clinically, in the percentage of headaches that the patients who received neurotoxin reported as being severe. Some patients may have additional benefit of neurotoxin therapy with second and perhaps third injection sequences.” Dr. Schreiber, Associate Medical Director of the Headache Care Center in Springfield, Missouri, presented his findings at the 56th Annual Meeting of the American Academy of Neurology.

THE IMPACT OF MIGRAINE

Prior clinical trials have reported on the potential of botulinum toxin in treating patients with migraine, but it has not been clear exactly how and which patients are best suited for the treatment, Dr. Schreiber noted. “The main objective of our study was to look at headache impact, to look at disability measures,” he declared. “In fact, a more traditional end point of preventive studies is the number of headache attacks that occur. But disability is often the starting point for therapy in clinical practice. That’s one of the decision points that we all make when we are addressing our patients.”

The investigators enrolled patients with disabling headache, according to the Headache Impact Test (HIT-6) (score of 60 or greater) and the Migraine Disability Assessment Scale (MIDAS) (score of 20 or greater). A total of 57 patients participated, all of whom were 18 or older and had a history of headaches for at least six months, with and without aura, and significant migraine-related disability.

Subjects were randomized to receive 139 units of botulinum toxin type A or placebo at 13 injection sites. Patients were injected after a one-month baseline period and again at month 4. They were assessed every 30 days throughout an eight-month evaluation period; 42 patients had complete data in at least four of eight months. “Those who were on placebo were given an open-label injection at the end, so there was an incentive to continue in the study,” Dr. Schreiber said. The primary outcome measure was change in headache-related impact for disability as measured by HIT-6 and MIDAS; secondary outcomes included headache intensity and subject satisfaction with treatment.

“The baseline characteristics of the patients who were enrolled in the study were fairly homogenous,” noted Dr. Schreiber. “There was a slight difference in age between the botulinum toxin and placebo groups, but otherwise there was a fair mix of patients in both groups. It’s important to note that they all had very significant headache-related disability.”

TREATMENT BENEFITS

The study revealed a “significant drop [in impact scores] in the first month in those who received botulinum toxin that held strong over the first four months,” said Dr. Schreiber. The overall HIT-6 score decreased from 66.5 (severe) to 59 (some impact). “There were some fluctuations in the placebo group, but overall there wasn’t a huge change,” he added. “When we looked at this from a statistical basis, looking at the change in HIT-6 from the baseline, the HIT-6 did drop some across the placebo group. But in the botulinum toxin group, there was a greater drop. When statistical analysis was done, it was statistically significant in several, although not all, time points across the course of the study.”

MIDAS scores dropped by 49% in patients receiving botulinum toxin (from 74 to 38). “There was some drop as well in the placebo group, and overall at the end there was not a statistical difference between the groups,” Dr. Schreiber noted. “But as we looked across the course of the study we thought that there was a drop in disability as measured by MIDAS.”

The percentage of severe headaches in the botulinum toxin group decreased from 32% of all headaches at baseline to 13% at eight months. “There appeared to be a progressive benefit from a repeated botulinum toxin treatment after four months,” Dr. Schreiber said. Patients taking placebo had no changes in headache severity, minimal HIT-6 score changes, and a 24-point decline in MIDAS. Adverse events were “generally mild and transient” and included injection site pain, rash, numb forehead, and soreness of the head, neck, or jaw in seven patients.

NEUROTOXIN VERSUS PLACEBO

“Our data support the concept that there was a reduction in migraine-related impact across this trial as measured by MIDAS and HIT-6,” Dr. Schreiber commented. “Patient satisfaction was significant, and in this trial there were no [major] adverse events. [Patients] maintained the effect over the course of eight months, and the fact that it did appear that there were less severe headaches … may speak to the continued effect of medication and against the placebo effect.” However, he cautioned, “Of course, in this kind of study, you always have to wonder about placebo.” He noted that some patients in the study initially seemed to be satisfied with the placebo. “But overall, there was a fairly consistent expression of satisfaction with the neurotoxin therapy.”

Furthermore, in noting some of his study’s limitations, “We didn’t have data across all patients at all time points,” in addition to the slight age differences between groups, Dr. Schreiber acknowledged. “Although there was a procedure done, and there were saline injections given, patients who watch television know what to look for. As investigators, we counsel the patients and say that there may or may not be that effect.… That is a problem when you are looking at placebo- controlled trials for this type of treatment.”

NR

—Colby Stong

Suggested Reading
Behmand RA, Tucker T, Guyuron B. Single-site botulinum toxin type A injection for elimination of migraine trigger points. Headache. 2003;43:1085-1089.
Ondo WG, Vuong KD, Derman HS. Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study. Cephalalgia. 2004;24:60-65.

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