- Top of page
- SUBJECTS AND METHODS
Objective.—To assess the safety and efficacy of botulinum toxin type A (BOTOX; Allergan, Inc) in the prevention of migraine.
Background.—Current migraine preventive therapies are often unsatisfactory because of their limited efficacy, adverse effects, and drug interactions. Botulinum toxin type A injections often reduce the pain associated with conditions such as cervical dystonia, achalasia, rectal fissures, and myofascial pain syndrome. An open-label, noncontrolled study of botulinum toxin type A suggested benefits for patients with migraine.
Design and Methods.—This was a double-blind, vehicle-controlled study of 123 subjects with a history of two to eight moderate-to-severe migraine attacks per month, with or without aura. Participants were randomized to receive single administrations of vehicle or botulinum toxin type A, 25 U or 75 U, injected into multiple sites of pericranial muscles at the same visit. During a 1-month baseline period and for 3 months following injection, subjects kept daily diaries in which they recorded migraine frequency, migraine severity, and the occurrence of migraine-associated symptoms.
Results.—Compared with vehicle treatment, subjects in the 25-U botulinum toxin type A treatment group showed significantly fewer migraine attacks per month, a reduced maximum severity of migraines, a reduced number of days using acute migraine medications, and reduced incidence of migraine-associated vomiting. Both the 25-U and 75-U botulinum toxin type A groups were significantly better than the vehicle group on subject global assessment. Botulinum toxin A treatment was well tolerated, with only the 75-U treatment group exhibiting a significantly higher rate of treatment-related adverse events than vehicle.
Conclusions.—Pericranial injection of botulinum toxin type A, 25 U, was found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.
Botulinum toxin type A (BTX-A) has been used clinically for a number of disorders believed to be due to overactive striated or smooth muscles, such as cervical dystonia, 1 blepharospasm, 2 spasticity, 3,4 rectal sphincter spasm with fissure, 5 and achalasia. 6 Benefits have also been reported for hyperhidrosis, 7 showing that BTX-A can inhibit overactive nonmotor as well as motor peripheral acetylcholine neurons. In addition to reducing muscle hyperactivity and spasm, BTX-A treatment often reduces the pain associated with cervical dystonia, achalasia, and rectal fissures. Preliminary evidence suggests that it may also be beneficial in the treatment of chronic low back pain associated with muscle spasm. 8
A recent open-label, noncontrolled study reported that treatment of patients with BTX-A markedly reduced migraine frequency and symptoms. 9 Our study attempted to confirm these findings by examining the safety and efficacy of BTX-A in the prevention of migraine, using a double-blind, vehicle-controlled design.
- Top of page
- SUBJECTS AND METHODS
In our study, injection of a total dose of BTX-A, 25 U, into three pericranial muscle groups was significantly superior to vehicle in reducing migraine frequency and severity, the use of acute migraine medication, and migraine-associated vomiting. The beneficial effects of BTX-A were observed mainly at 2 and 3 months posttreatment, as has been reported for other preventive migraine treatments. 10 This is consistent with reports that botulinum toxin requires up to 3 weeks to achieve its maximum effect. 11 Improvement produced by BTX-A continues through month 3, suggesting continued improvement beyond 3 months. The 75-U dose of BTX-A did not perform as well as the 25-U dose in our study, perhaps due to the lower frequency of migraines at baseline in this treatment group. Botulinum toxin type A treatment is safe for migraine: only the 75-U BTX-A group exhibited significantly more treatment-related adverse effects than the vehicle group.
The potential efficacy of BTX-A in the treatment of migraine raises interesting questions regarding the role of muscle contraction in the pathophysiology of migraine 12 and the mechanism of action of botulinum toxin treatment in pain disorders in general. The simplest explanation is as follows: pericranial muscle contractions somehow contribute to the migraine triggering process and BTX-A reduces migraine frequency and severity by reducing these contractions. However, since botulinum toxins are general exocytotic inhibitors, 13 the possibility exists that botulinum toxin inhibits pain pathways through some, as yet unknown, effect on the sensory system.
These preliminary results suggest that treatment with BTX-A may be useful in the prevention of migraine. Further studies are needed to determine optimal dosing and injection sites, optimal patient characteristics, and functional benefits that affect patient quality of life.
Acknowledgments: Financial support was provided by Allergan, Inc.
The BOTOX® Migraine Clinical Research Group: Sheena Aurora, MD and K.M.A. Welch, MD (Henry Ford Hospital, Detroit, Mich); Roger Cady, MD and Dale Carter, MD (Headache Care Center, Springfield, Mo); Jack Klapper, MD (Colorado Neurology and Headache Center, Denver, Colo); David Kudrow, MD (California Medical Clinic for Headache, Encino, Calif); Elizabeth Loder, MD (Spaulding Rehabilitation Hospital, Boston, Mass); Joseph Nicolas, MD and Nabih Ramadan, MD (Cincinnati Headache Center, Cincinnati, Ohio); Egilius Spierings, MD (Boston Clinical Research Center, Wellesley Hills, Mass); Thomas Ward, MD (Dartmouth-Hitchcock Medical Center, Lebanon, NH); Paul Winner, DO (Premiere Research Institute, West Palm Beach, Fla); and Ron DeGryse, MS, Nina Eadie, MBA, and Eric Chun, BS, CCRA (Allergan, Inc, Irvine, Calif).