title: Placebo and nocebo responses in randomised controlled trials of drugs applying for approval for fibromyalgia syndrome treatment: systematic review and meta-analysis.
abstract: OBJECTIVE
  The superiority of true drug treatment over placebo in reducing symptoms of fibromyalgia syndrome (FMS) is small and bought by relevant rates of drop-outs due to adverse events. Recent systematic reviews demonstrated that a substantial proportion of the beneficial and adverse effects of true drug is attributable to placebo in chronic pain trials. We determined the magnitude of the placebo and nocebo response and its impact on the benefits and harms of true drug in trials of drugs which were submitted for approval for treatment of FMS.
  
  
  METHODS
  CENTRAL, MEDLINE and clinicaltrials.gov were searched from inception to June 30, 2012 for randomized double-blind placebo controlled trials with a parallel design for duloxetine, milnacipran, pregabalin and sodium oxybate in FMS-patients. The magnitude of placebo response was assessed by the pooled estimate of a 50% placebo pain reduction. The magnitude of nocebo response was determined by the pooled estimate of drop-out rates due to adverse events in placebo groups.
  
  
  RESULTS
  18 studies with 3546 patients on placebo were included. The pooled estimate of a 50% pain reduction by placebo was 18.6% (95% CI 17.4 to 19.9%). The pooled estimate of drop-out due to adverse events in placebo groups was 10.9% (95% CI 9.9 to 11.9%).
  
  
  CONCLUSIONS
  The magnitude of placebo and nocebo response in trials of drugs applying for approval for FMS treatment was substantial. Study investigators aim to reduce placebo response. By contrast, clinicians often utilise placebo effects. Strategies to reduce nocebo responses in clinical trials and practice should be developed.
authors.affiliation: Department of Internal Medicine I, Klinikum Saarbrücken, Saarbrücken, Germany. whaeuser@klinikum-saarbruecken.de
authors.forename: Winfried
authors.initials: W
authors.lastname: Häuser
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Tölle
authors.forename: Fred
authors.initials: F
authors.lastname: Wolfe
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D059350:Chronic Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D017277:Drug Approval; D005260:Female; D005356:Fibromyalgia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D058748:Pain Perception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010352:Patient Dropouts; D015990:Placebo Effect; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000700:Analgesics