title: Preventive pharmacologic treatments for episodic migraine in adults.
abstract: OBJECTIVE
  Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.
  
  
  METHODS
  Electronic databases through May 20, 2012.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  We did not quantify reporting bias or contact principal investigators regarding unpublished trials.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.
authors.affiliation: Minnesota Evidence-based Practice Center, Minneapolis, MN 55455, USA. shaml005@umn.edu
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Shamliyan
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Rema
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Jennifer Biggs
authors.initials: JB
authors.lastname: Miller
authors.forename: Shi-Yi
authors.initials: SY
authors.lastname: Wang
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Taylor
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kane
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D008881:Migraine Disorders / Q000517:prevention & control*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants