title: Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis.
abstract: OBJECTIVE
  When analyzing results of randomized clinical trials, the treatment with the greatest specific effect compared with its placebo control is considered to be the most effective one. Although systematic variations of improvements in placebo control groups would have important implications for the interpretation of placebo-controlled trials, the knowledge base on the subject is weak.
  
  
  OBJECTIVE
  To investigate whether different types of placebo treatments are associated with different responses using the studies of migraine prophylaxis for this analysis.
  
  
  METHODS
  We searched relevant sources through February 2012 and contacted the authors to identify randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group. We calculated pooled random-effects estimates according to the type of placebo for the proportions of treatment response. We performed meta-regression analyses to identify sources of heterogeneity. In a network meta-analysis, direct and indirect comparisons within and across trials were combined. Additional analyses were performed for continuous outcomes.
  
  
  METHODS
  Active migraine treatment and the placebo control conditions.
  
  
  METHODS
  Proportion of treatment responders, defined as having an attack frequency reduction of at least 50%. Other available outcomes in order of preference included a reduction of 50% or greater in migraine days, the number of headache days, or headache score or a significant improvement as assessed by the patients or their physicians.
  
  
  RESULTS
  Of the 102 eligible trials, 23 could not be included in the meta-analyses owing to insufficient data. Sham acupuncture (proportion of responders, 0.38 [95% CI, 0.30-0.47]) and sham surgery (0.58 [0.37-0.77]) were associated with a more pronounced reduction of migraine frequency than oral pharmacological placebos (0.22 [0.17-0.28]) and were the only significant predictors of response in placebo groups in multivariable analyses (P = .005 and P = .001, respectively). Network meta-analysis confirmed that more patients reported response in sham acupuncture groups than in oral pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30-2.72]). Corresponding analyses for continuous outcomes showed similar findings.
  
  
  CONCLUSIONS
  Sham acupuncture and sham surgery are associated with higher responder ratios than oral pharmacological placebos. Clinicians who treat patients with migraine should be aware that a relevant part of the overall effect they observe in practice might be due to nonspecific effects and that the size of such effects might differ between treatment modalities.
authors.affiliation: Institute of General Practice, Klinikum rechts der Isar, Technische Universität München, Munich, Germany2Institute of Medical Psychology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Meissner
authors.forename: Margrit
authors.initials: M
authors.lastname: Fässler
authors.forename: Gerta
authors.initials: G
authors.lastname: Rücker
authors.forename: Jos
authors.initials: J
authors.lastname: Kleijnen
authors.forename: Asbjorn
authors.initials: A
authors.lastname: Hróbjartsson
authors.forename: Antonius
authors.initials: A
authors.lastname: Schneider
authors.forename: Gerd
authors.initials: G
authors.lastname: Antes
authors.forename: Klaus
authors.initials: K
authors.lastname: Linde
mesh_terms: D015670:Acupuncture Therapy; D004334:Drug Administration Schedule; D006801:Humans; D008881:Migraine Disorders / Q000517:prevention & control* / Q000628:therapy*; D019635:Neurosurgical Procedures; D015990:Placebo Effect; D010919:Placebos / Q000008:administration & dosage / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D010919:Placebos