title: Adverse events attributable to nocebo in randomized controlled drug trials in fibromyalgia syndrome and painful diabetic peripheral neuropathy: systematic review.
abstract: OBJECTIVE
  The objectives of the study were to determine the impact of nocebo effects on adverse events (AEs) in drug trials in fibromyalgia syndrome (FMS) and painful diabetic peripheral neuropathy (DPN).
  
  
  METHODS
  MEDLINE, CENTRAL, SCOPUS, and the databases of the U.S. National Institutes of Health and the Pharmaceutical Research and Manufacturers of America were searched until December 31, 2010. Randomized controlled trials with a parallel design of any drug therapy compared with pharmacological placebo in patients with FMS and DPN were included. Pooled estimates of nocebo effects (number of patients with at least 1 AE and dropping out due AEs) were calculated for placebo and true drug groups by a random effects model.
  
  
  RESULTS
  Fifty-eight FMS (62 DPN) trials included a total of 5065 (5095) patients in placebo groups. The quality of reporting the assessment strategy of AEs was poor in most trials. The pooled estimate of the event rate drop out rate due to AEs in placebo groups was 9.6 [95% confidence control (CI): 8.6-10.7] in placebo and 16.3 (95% CI: 14.1-31.2) in true drug groups of FMS trials and was 5.8 (95% CI: 5.1-6.6) in placebo and 13.2 (95% CI: 10.7-16.2) in true drug groups of DPN trials. Nocebo effects accounted for 72.0% (44.9) of the drop outs in true drug groups in FMS (DPN).
  
  
  CONCLUSIONS
  Nocebo effects substantially accounted for AEs in drug trials of FMS and DPN. Standards to assess and report AEs should be defined by regulatory agencies. Strategies to minimize nocebo effects in both clinical trials and clinical practice should be developed.
authors.affiliation: Department of Internal Medicine I, Klinikum Saarbrücken, Winterberg 1, Saarbrücken, Germany. whaeuser@klinikum-saarbruecken.de
authors.forename: Winfried
authors.initials: W
authors.lastname: Häuser
authors.forename: Claas
authors.initials: C
authors.lastname: Bartram
authors.forename: Eva
authors.initials: E
authors.lastname: Bartram-Wunn
authors.forename: Thomas
authors.initials: T
authors.lastname: Tölle
mesh_terms: D000328:Adult; D000700:Analgesics / Q000009:adverse effects* / Q000627:therapeutic use; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004311:Double-Blind Method; D017277:Drug Approval; D004345:Drug Industry; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement; D015990:Placebo Effect; D017594:Publication Bias; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D015203:Reproducibility of Results; D012107:Research Design; D012109:Research Support as Topic; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000700:Analgesics