Injections of botulinum toxin A may be of some benefit in preventing chronic migraine and chronic daily headaches, but that benefit is small and does not extend to episodic migraine, episodic tension-type headaches, or chronic tension-type headaches, according to a report in the April 25 issue of JAMA.
In a metaanalysis of 31 randomized controlled trials, botulinum toxin A injections reduced the number of chronic migraine headaches from 19.5 to 17.2 per month and the number of chronic daily headaches from 17.5 to 15.4 per month, differences of unknown clinical importance. The treatment did not reduce the frequency of other types of headache, said Dr. Jeffrey L. Jackson of the Zablocki Veterans Affairs Medical Center and the Medical College of Wisconsin, Milwaukee, and his associates.
"Our finding of minimal benefit is contrary to findings from case series and open-label studies that suggested substantial benefits. These differences in results may be due to a strong association of placebo with improved outcomes and the natural history of headaches, in which improvement is observed over time," they noted.
Dr. Jackson and his colleagues searched the literature for randomized clinical trials of at least 4 weeks’ duration that compared botulinum toxin A injections against either placebo injections or prophylactic medications.
In 27 placebo-controlled trials involving adults, the average subject age was 42 years and the average duration of the study was 19 weeks (range, 84-270 days). A total of 1,938 of these subjects had episodic migraines, 1,544 had chronic migraines, 616 had chronic tension-type headaches, and 1,115 had chronic daily headaches.
Botulinum A injections were associated with a reduction of approximately two headaches per month for both chronic migraine and chronic daily headaches, but did not reduce the other types of headache. Moreover, there was a "substantial" placebo effect among control subjects, with a significant number of them reporting reduced headaches over time.
The researchers also analyzed four trials that compared the injections against prophylactic medications. Botulinum toxin A injections were no more effective than were topiramate, amitriptyline, or valproate at preventing any type of headache.
The injections did reduce headache severity in a single trial comparing them against methylprednisolone, but given that corticosteroids are not generally used for headache prophylaxis, "it is unclear how useful this comparison is clinically," Dr. Jackson and his associates said (JAMA 2012;307:1736-45).
Study subjects who received botulinum toxin A injections were more likely to report adverse effects than were those who received placebo injections, including blepharoptosis, muscle weakness, neck pain, neck stiffness, paresthesia, and skin tightness.
Outcomes with botulinum toxin A injections were the same regardless of whether they were administered on a fixed or a flexible schedule, whether particular muscle groups were injected, or whether injection sites were selected on the basis of patients’ pain reports. Outcomes also were the same whether the injections were performed once, or three times at 90-day intervals.
There also were no differences in outcomes according to the number of muscle groups injected or the total dose of botulinum toxin A administered, the investigators added.
Among the study’s limitations was the fact that for nearly all the headache subtypes, there were relatively few studies and may of the studies were small.
No relevant financial conflicts of interest were reported.