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Preventive Pharmacologic Treatments for Episodic Migraine in Adults



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


Electronic databases through May 20, 2012.


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.


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


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.


We did not quantify reporting bias or contact principal investigators regarding unpublished trials.


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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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.


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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Systematic review registration no.: CRD42012001918

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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).

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  • migraine
  • evidence based medicine
  • adverse drug effects