title: A critical review of exercise as a treatment for clinically depressed adults: time to get pragmatic.
abstract: OBJECTIVE
  Although considerable evidence supports the efficacy of exercise as an antidepressant treatment, critical reviews informing routine practice and future research directions are scarce.
  
  
  METHODS
  We critically reviewed exercise studies for clinically depressed adults, focussing on the PICOS criteria referred to participants, interventions, comparisons, outcomes, and study designs.
  
  
  RESULTS
  Most studies have not screened their samples for symptom heterogeneity. Also, they have employed heterogeneous exercise interventions and control groups that may lead to an underestimation of the benefits of exercise. In addition, pragmatic trials allowing scalable replication and implementation in routine practice are scarce. Future studies, can consider the research domain criteria as a diagnostic framework, and conduct moderator analyses to identify depressed subgroups with symptomatology and biopsychosocial characteristics associated with differential responses to exercise interventions. The search for biomarkers of the antidepressant responses to exercise should be prioritised. Further, non-physically active comparison groups should be used to minimise treatment cross-overs and thus the underestimation of the effects of exercise interventions. Finally, the use of outcome measures that maintain their validity at low and moderate levels of symptom severity and the development of trials with a pragmatic design are essential.
  
  
  CONCLUSIONS
  The current evidence base is fraught with methodological considerations that need to be taken into account in order to increase further our understanding on the impact of exercise as medicine in depression. Future research should include moderator analyses, incorporate biomarker assays, use appropriate control and comparison groups, assess outcomes with psychometrically sensitive measures, and prioritise pragmatic trials towards transition to routine practice.
authors.affiliation: 1Post-Graduation Program of Medical Sciences: Psychiatry,Federal University of Rio Grande do Sul,Porto Alegre,Brazil.
authors.forename: Felipe Barreto
authors.initials: FB
authors.lastname: Schuch
authors.affiliation: 2Exercise Psychology and Quality of Life Laboratory,Department of Physical Education and Sport Science,University of Thessaly,Trikala,Greece.
authors.forename: Ioannis Dimitrios
authors.initials: ID
authors.lastname: Morres
authors.affiliation: 3Department of Kinesiology,Iowa States University,Ames,IA,USA.
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Ekkekakis
authors.affiliation: 4School of Psychiatry,University of New South Wales,Sydney,Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Rosenbaum
authors.affiliation: 6Physiotherapy Department,South London and Maudsley NHS Foundation Trust,Denmark Hill,London,UK.
authors.forename: Brendon
authors.initials: B
authors.lastname: Stubbs
mesh_terms: D003866:Depressive Disorder / Q000175:diagnosis / Q000628:therapy*; D005081:Exercise Therapy; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
keywords: depression; exercise; physical activity; review; treatment