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Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine
  1. Clare P Herd1,
  2. Claire L Tomlinson2,
  3. Caroline Rick3,
  4. William J Scotton4,
  5. Julie Edwards5,
  6. Natalie J Ives2,
  7. Carl E Clarke6,
  8. AJ Sinclair4
  1. 1 Institute of Applied Health Research, University of Birmingham, Birmingham, UK
  2. 2 BCTU, University of Birmingham, Birmingham, UK
  3. 3 Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, Nottinghamshire, UK
  4. 4 University of Birmingham, Institute of Metabolism and Systems Research, Birmingham, UK
  5. 5 Sandwell and West Birmingham Hospitals NHS Trust, Department of Neurology, Birmingham, Birmingham, UK
  6. 6 University of Birmingham, Neurology, Birmingham, UK
  1. Correspondence to Dr AJ Sinclair; a.b.sinclair{at}


Objectives To assess the effects of botulinum toxin for prevention of migraine in adults.

Design Systematic review and meta-analysis.

Data sources CENTRAL, MEDLINE, Embase and trial registries.

Eligibility criteria We included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache.

Data extraction and synthesis Cochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed.

Results Twenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of −2.0 migraine days/month (95% CI −2.8 to −1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of −2.70 cm (95% CI −3.31 to −2.09, n=75) and −4.9 cm (95% CI −6.56 to −3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes.

Conclusions In chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.

  • migraine disorders
  • botulinum toxin
  • botox
  • systematic review
  • randomised controlled trial

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  • Contributors C Clarke and A Sinclair conceived the review. C Herd ran searches not covered by the review group’s information specialist. C Herd, C Tomlinson, C Rick and A Sinclair screened the search results. C Herd, C Tomlinson, C Rick, W Scotton, C Clarke and A Sinclair assessed the quality of studies and extracted data. C Herd contacted trial authors, managed data and entered it into RevMan, and carried out data analysis. N Ives provided statistical advice. C Herd, C Tomlinson, C Rick, N Ives, C Clarke and A Sinclair were involved in interpretation of the results. All authors read and edited final version of the review.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests Yes, there are competing interests for one or more authors and I have provided a Competing Interests statement in my manuscript.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Full data analysis and trial summaries available in Cochrane review DOI: 10.1002/14651858.CD011616.pub2.