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Preventive Pharmacologic Treatments for Episodic Migraine in Adults

Abstract

OBJECTIVES

Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.

DATA SOURCES

Electronic databases through May 20, 2012.

ELIGIBILITY CRITERIA

English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life.

STUDY APPRAISAL AND SYNTHESIS METHODS

We assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis.

RESULTS

Of 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200–400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention.

LIMITATIONS

We did not quantify reporting bias or contact principal investigators regarding unpublished trials.

CONCLUSIONS

Approved drugs prevented episodic migraine frequency by ≥50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for long-term effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.

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Acknowledgments

Contributors

We would like to thank the librarians, Judy Stanke, MA, and Delbert Reed, PhD, for their contributions to the literature search; Jeannine Ouellette for her help in writing the report; Marilyn Eells for editing and formatting the report; and Christa Prodzinski, RN, and Kirsten Johnson, BS, for assistance with data entry, quality control, and formatting tables. We would like to thank Hwanhee Hong, PhD candidate, for her help in conducting Bayesian network meta-analyses.

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Prepared by the University of Minnesota Evidence-based Practice Center under contract no. 290-2007-10064 I with the AHRQ

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The authors declare that they do not have a conflict of interest.

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Correspondence to Tatyana A. Shamliyan MD, MS.

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Shamliyan, T.A., Choi, JY., Ramakrishnan, R. et al. Preventive Pharmacologic Treatments for Episodic Migraine in Adults. J GEN INTERN MED 28, 1225–1237 (2013). https://doi.org/10.1007/s11606-013-2433-1

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KEY WORDS

  • migraine
  • evidence based medicine
  • adverse drug effects