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Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis
  1. Jesper Krogh1,
  2. Carsten Hjorthøj1,
  3. Helene Speyer1,
  4. Christian Gluud2,
  5. Merete Nordentoft1
  1. 1 Faculty of Health Sciences, Mental Health Centre Copenhagen, University of Copenhagen, Copenhagen, Denmark
  2. 2 Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  1. Correspondence to Dr Jesper Krogh; jesper.krogh{at}


Objectives To assess the benefits and harms of exercise in patients with depression.

Design Systematic review

Data sources Bibliographical databases were searched until 20 June 2017.

Eligibility criteria and outcomes Eligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention.

Results Thirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes.

Conclusions Trials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes.

Systematic review registration The protocol was published in the journal Systematic Reviews: 2015; 4:40.

  • Exercise
  • Systematic Review
  • Meta-analysis
  • Evidence Based Medicine
  • Randomised Clinical Trials

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  • Contributors JK conceived the project, collected data, did the statistical analysis, analysed the data, drafted and revised the manuscript. He is guarantor. CH collected the data, analysed the data and revised the manuscript. HS conceived the project, collected data, analysed the data and revised the manuscript. CG conceived the project, analysed the data and revised the manuscript. MN conceived the project, analysed the data and revised the manuscript.

  • Competing interests K, CG, and MN have previously published two trials and a meta-analysis on this topic, which could introduce an academic bias in the current systematic review. We asked new authors (HS and CH) to be involved in the preparation of the protocol, trial selection and bias assessment. No support from any organisation was received for the submitted work; no financial relationship with any organisations that might have an interest in the submitted work in the previous three years; and apart from the above no other relationship or activities that could appear to have influenced the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data used in this study are available in figures and tables. No other data were used.

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