What is the efficacy of botulinum toxin (BTX) for the treatment of chronic daily headaches?

Updated: Jun 19, 2018
  • Author: Anthony H Wheeler, MD; Chief Editor: Meda Raghavendra (Raghu), MD  more...
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Chronic daily headache is estimated to effect 4% of the US population. [136, 137] This phenomenon was originally conceived and described as a disorder that developed in individuals with a long history of episodic migraines or tension-type headaches. [138] Transformed or chronic migraine was a concept introduced by Mathew et al to describe a clinical syndrome which evolves gradually from typical migraine events in patients who usually have onset of symptoms in their early twenties and who characteristically develop increasing frequency and reduced intensity of headaches. [115]

In contrast and by definition, chronic tension-type headache characteristically develops in patients with a history of headaches that are not associated with distinct migraine features such as nausea, photophobia, and phonophobia. Although most transformations occur slowly, sudden conversion may occur in 20% of cases, and often follows trauma, illness, or surgery. [139]

In an open-label study by Klapper and Klapper, 4 of 5 treated patients with chronic daily headache benefited from BTX-A injections. [140] In a follow-up randomized study, 56 patients with chronic daily headache were divided into 4 groups, depending on whether they received forehead and/or suboccipital BTX-A injections. Only the patients who received BTX-A injections into both regions experienced a significant benefit. Argoff reported 3 patients with chronic daily headache who were all treated successfully using a total dose of 5000 U of BTX-B injected into the frontalis, temporalis, corrugator, splenius capitis, splenius cervicis, levator scapular, and trapezius muscles. [141]

A randomized, double-blind, placebo-controlled, parallel design study looked at the use of BTX-A for treating chronic daily headache in patients who were experiencing either or both chronic migraine or tension-type headache. [142] Sixty patients satisfying criteria for this disorder were randomized to receive either placebo or 200 U of BTX-A using the "follow the pain" injection paradigm. If the patient consented, a second open-label BTX-A injection treatment was provided at 12 weeks. After the first injection session, patients treated with BTX-A had significantly fewer headache days during weeks 8-12 compared with the subjects who received just placebo. Twenty-four patients who received 2 BTX-A treatment sessions had significantly fewer headache days over the 12-week study period than those who received BTX-A injections only once.

Mathew et al performed a randomized, double-blind, placebo-controlled trial of 355 patients with chronic daily headaches due to chronic migraine or tension-type headache. [143] Again, findings showed a dramatic benefit with treated patients having an average of approximately 7 more headache-free days per month compared with baseline. In addition, a statistically significant percentage of patients in the treatment group experienced a 50% or greater reduction in the frequency of headache days. Both studies reported a small number of transient mild to moderate adverse events.

Another double-blind, placebo-controlled trial using BTX-A enrolled 702 patients. [144] The overall study duration was 11 months and included a 30-day screening period followed by a 30-day placebo run-in. Subjects determined as placebo responders and nonresponders were randomized into placebo or BTX-A treatment groups of 225 U, 150 U, or 75 U. Patients received additional masked treatments at 90 days and 180 days. Participants were assessed every 30 days for 9 months. The primary efficacy endpoint was a mean change from their baseline frequency of headache-free days at day 180 compared with the placebo nonresponder group. This primary efficacy endpoint was not met; all groups responded to treatment. However, the 225 U and 150 U groups experienced a greater reduction in headache frequency than the placebo group at day 240.

Five randomized, double-blind, placebo-controlled studies all demonstrated clinically significant reduction in the frequency of chronic recurrent migraine headaches using BTX-A. [145, 146, 147, 148, 149, 119] In some studies, BTX-A was the only prophylactic therapy. Other promising findings included reduction of acute medication use, reduced frequency of long duration headaches, and increased headache-free days.

A randomized, double-blind, placebo-controlled, exploratory study by Saper et al demonstrated that prophylactic treatment with BTX-A reduced the frequency of headaches in migraineurs with chronic daily headache who were overusing acute headache pain medications. [119] These findings may indicate that chronic migraine or BTX might be promising as a treatment for patients with medication overuse headache.

In general, several reviews aimed at the use of BTX-A for the management of headache disorders were favorable, and all reviewers suggested additional research was necessary to confirm clinical observations that have been made to date. [150, 117, 112, 151] Two reviews, using an evidence-based analysis, concluded that the evidence supporting BTX treatment for migraine was insufficient to date; nevertheless, the same authors acknowledged the probability that certain subgroups of migraine headache patients were likely shown to be responsive to BTX treatment. [151, 150]

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