What is the efficacy of botulinum toxin A (BTX-A) injections for the treatment of episodic migraine headaches?

Updated: Jun 19, 2018
  • Author: Anthony H Wheeler, MD; Chief Editor: Meda Raghavendra (Raghu), MD  more...
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However, evidence of benefit from BTX was not as clearly demonstrated in 3 double-blind, randomized, placebo-controlled studies. Relja et al randomized patients with episodic migraine occurring between 3-15 days per month after a single-blind, 30-day, placebo run-in. [118] Patients were randomized within placebo responder or nonresponder strata into placebo and 3 BTX-A treatment groups of 225 U, 150 U, or 75 U. A fixed-site, fixed-dose injection methodology was used for 3 treatment sessions at 90-day intervals. The primary efficacy measure was a mean change from baseline of episodic migraine frequency between day 150 and day 180 in the placebo nonresponder strata.

Four hundred and ninety-five patients (322 placebo nonresponders) were randomized into 1 of the 3 BTX-A treatment groups or placebo. All placebo and BTX-A treated groups showed substantial reductions in episodic migraine frequency; however, no statistically significant differences were seen among treatment groups. Results may have been confounded by study participants who overused acute rescue and abortive medications.

Saper et al performed a randomized, double-blind, placebo-controlled study of 232 patients with 4-8 moderate to severe episodic migraine headaches per month. [119] Patients were randomized into placebo or 1 of 4 BTX-A treatment groups. Three BTX-A groups consisted of patients receiving a single injection in the frontal, temporal, or glabellar regions; a fourth group received therapeutic injections into all 3 areas. For 3 months following a single injection session, patients recorded pertinent evaluation variables and periodically completed quality of life questionnaires. All BTX-A groups and the placebo group showed a comparable reduction in the frequency of episodic migraine from baseline, but no significant between-group differences were observed for any of the multiple efficacy measures for treatment. Again, study results were likely confounded by excessive patient use of concomitant prophylactic and acute headache medications.

In a third randomized, placebo-controlled study by Elkind et al, patients with 4-8 moderate to severe episodic migraines per month were randomized into placebo or into one of 3 BTX-A treatment groups receiving 7.5 U, 25 U, or 50 U. [120] Injections were placed into predetermined fixed sites in the frontal, glabellar, and temporal muscles. Patients were subjected to 3 injection cycles, 4 months apart. Patients receiving placebo or 7.5 U were then randomized into a second study to receive a masked higher dose of 25 U or 50 U. Patients in the initial 25 U and 50 U groups received 2 masked treatment sessions of their previously assigned dose. Patients completing the second study arm were next randomized into another 3 treatment groups: BTX-A 25 U, 50 U, or placebo.

In the first randomized study-arm, all groups showed a comparable reduction in frequency of episodic migraine at all time points; however, the BTX-A groups demonstrated statistically significant improvement over the placebo group for global assessment at 4 months. Improvements in all groups observed in the first study were sustained through both the second and third arms of the study. Therefore, this study failed to show a significant reduction in frequency of migraine compared with placebo, which the investigators determined was the primary reason for prescribing a prophylactic migraine therapy. However, result validity was again questioned due to excessive patient use of prophylactic and acute headache medications.

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