title: The placebo response in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis.
abstract: OBJECTIVE
  The placebo response is conventionally asserted to be high in chronic fatigue syndrome (CFS) because of the latter's subjective nature and obscure pathogenesis, but no systematic review of placebo responses has been undertaken. We report such a study. Patient expectation is known to be important in the placebo response. It is also known that CFS patients attending specialist clinics often have strong physical attributions regarding causation and hence skepticism about psychological or psychiatric interventions. If so, the placebo response in CFS may be influenced by the type of intervention according to its perceived rationale. We aimed to estimate the summary placebo response in clinical trials of CFS and to determine whether intervention type influences the placebo response in CFS.
  
  
  METHODS
  We searched Medline, Embase, Cochrane Library, PsychInfo, and the references of the identified articles, and contacted experts for controlled trials (randomized or nonrandomized) of any intervention on CFS patients reporting the placebo response as a clinical improvement in physical or general outcomes. Data were extracted from the articles and validity assessment conducted by one reviewer and checked by a second. Meta-analysis and metaregression were performed.
  
  
  RESULTS
  The pooled placebo response was 19.6% (95% confidence interval, 15.4-23.7), lower than predicted and lower than in some other medical conditions. The meta-regression revealed that intervention type significantly contributed to the heterogeneity of placebo response (p = .03).
  
  
  CONCLUSIONS
  In contrast with the conventional wisdom, the placebo response in CFS is low. Psychological-psychiatric interventions were shown to have a lower placebo response, perhaps linked to patient expectations.
authors.affiliation: Section of General Hospital Psychiatry, Institute of Psychiatry, King's College London, United Kingdom. h.cho@iop.kcl.ac.uk
authors.forename: Hyong Jin
authors.initials: HJ
authors.lastname: Cho
authors.forename: Matthew
authors.initials: M
authors.lastname: Hotopf
authors.forename: Simon
authors.initials: S
authors.lastname: Wessely
mesh_terms: D000328:Adult; D002648:Child; D015928:Cognitive Behavioral Therapy; D016001:Confidence Intervals; D018849:Controlled Clinical Trials as Topic; D005081:Exercise Therapy; D015673:Fatigue Syndrome, Chronic / Q000523:psychology / Q000628:therapy*; D006801:Humans; D015990:Placebo Effect; D012044:Regression Analysis; D016896:Treatment Outcome