title: Challenges Establishing the Efficacy of Exercise as an Antidepressant Treatment: A Systematic Review and Meta-Analysis of Control Group Responses in Exercise Randomised Controlled Trials.
abstract: BACKGROUND
  Whilst previous meta-analyses have demonstrated that control group responses (CGRs) can negatively influence antidepressant efficacy, no such meta-analysis exists in exercise randomised controlled trials (RCTs).
  
  
  OBJECTIVE
  The aim of this study was to conduct a systematic review and meta-analysis investigating CGRs and predictors in control groups of exercise RCTs among adults with depression.
  
  
  METHODS
  Three authors acquired RCTs from a previous Cochrane review (2013) and conducted updated searches of major databases from January 2013 to August 2015. We included exercise RCTs that (1) involved adults with major depressive disorder (MDD) or depressive symptoms; (2) measured depressive symptoms pre- and post-intervention using a validated measure [e.g. Hamilton Depression Scale (HAM-D)]; and (3) included a non-active control group. A random effects meta-analysis calculating the standardised mean difference (SMD) together with 95 % confidence intervals (CIs) was employed to determine CGR.
  
  
  RESULTS
  Across 41 studies, 1122 adults with depression were included [mean (SD) age 50 (18) years, 63 % female]. A large CGR of improved depressive symptoms was evident across all studies (SMD -0.920, 95 % CI -1.11 to -0.729). CGRs were elevated across all subgroup analyses, including high quality studies (n = 11, SMD -1.430, 95 % CI -1.771 to -1.090) and MDD participants (n = 18, SMD -1.248, 95 % CI = -1.585 to -0.911). The CGR equated to an improvement of -7.5 points on the HAM-D (95 % CI -10.30 to -4.89). In MDD participants, increasing age moderated a smaller CGR, while the percentage of drop-outs, baseline depressive symptoms and a longer control group duration moderated a larger CGR (i.e. improvement) (p < 0.05).
  
  
  CONCLUSIONS
  In order to demonstrate effectiveness, exercise has to overcome a powerful CGR of approximately double that reported for antidepressant RCTS.
authors.affiliation: Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK. brendonstubbs@hotmail.com.|Health Service and Population Research Department, Institute of Psychiatry, King's College London, De Crespigny Park, Box SE5 8AF, London, UK. brendonstubbs@hotmail.com.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Department of Rehabilitation Sciences, KU Leuven-University of Leuven, Leuven, Belgium.|KU Leuven-University of Leuven, Z.org Leuven, campus Kortenberg, Kortenberg, Belgium.
authors.forename: Davy
authors.initials: D
authors.lastname: Vancampfort
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Rosenbaum
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Ward
authors.affiliation: School of Public Health, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: Justin
authors.initials: J
authors.lastname: Richards
authors.affiliation: Population Health Research Institute, St. George's University of London, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Ussher
authors.affiliation: Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.|Graduate Program in Medical Sciences-Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Felipe B
authors.initials: FB
authors.lastname: Schuch
mesh_terms: D035061:Control Groups; D003866:Depressive Disorder / Q000628:therapy*; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic