There has been considerable research interest in the effects of exercise on depression over the past three decades and many systematic reviews have reported moderate to large effect sizes, with the standardised mean difference for the most recent Cochrane review being −0.82 (95% confidence interval −1.12 to −0.51).1 2 3 A new linked trial (TREAtment of Depression with physical activity (TREAD); doi:10.1136/bmj.e2758) adds to this evidence base.4
At first glance reviews suggest that exercise is effective in the treatment of depression. However, most trials included in systematic reviews recruited small numbers of patients, had a short follow-up, and did not adequately conceal randomisation or recruited non-clinical community volunteers (or both). Volunteers are more likely to be motivated to exercise and may be less severely depressed than people identified in clinical settings. Subgroup analyses that included only the higher quality trials in the Cochrane review reduced the effect size to −0.42 (−0.88 to 0.03),1 casting doubt on the main finding.
In 2009 the UK National Institute for Health and Clinical Excellence recommended that people with persistent subthreshold depressive symptoms or mild-moderate depression should be advised of the benefits of exercise,5 despite a lack of high quality evidence to support such a recommendation. The investigators in the current trial tried to remedy the methodological concerns of previous trials and answer definitively whether or not physical activity is an effective treatment in patients diagnosed with depression.4
TREAD was a large (n=361) methodologically rigorous trial that enrolled participants from primary care who presented with depression that had been confirmed by standardised clinical interview. The intervention was theory based and patient centred, and it aimed to be deliverable within the health service by physical activity facilitators, without unsustainable resource implications. TREAD compared usual care plus physical activity with usual care only and reported no significant difference in levels of depression between the groups at follow-up over one year.
These negative findings contrast with more positive findings from systematic reviews but are perhaps not surprising, particularly when considered alongside the results of a more recent meta-analysis of 13 trials that had recruited only patients with clinically diagnosed depression.6 This meta-analysis reported that physical exercise showed a small effect on depression (standardised mean difference −0.40, −0.66 to −0.14). However, no significant difference was found when the analysis was restricted to trials with follow-up beyond the end of the intervention (−0.01, −0.28 to 0.26) or to the three high quality trials (−0.19, −0.70 to 0.31), which suggests that exercise may not be effective in this population in the long term. Should we therefore conclude, on the basis of recent evidence, that physical activity has no effect on depression in clinical populations?4 6
Not necessarily. In the TREAD trial, usual care could comprise antidepressants, counselling, referral to exercise on prescription schemes, or referral to secondary care mental health services. Patients in both groups therefore already received high quality care, and 57% were taking antidepressants at recruitment. It may have been difficult for the addition of a physical activity intervention to make an appreciable difference. In addition, about 25% of participants were already meeting the current UK government guidelines for physical activity at baseline (the target level for the intervention),7 and they could feasibly have already been gaining any benefits that physical activity might provide, leaving little room for the intervention to make a difference.
Adherence was good, and 70% of participants received an adequate dose of the intervention, which is an achievement considering that it is difficult to motivate people who are depressed to commit to an exercise intervention.8 However, although a significant difference in physical activity between groups was reported at follow-up, this was relatively small and based on self reported data, which are prone to overestimation. The relatively severe depression of the recruited population (mean Beck depression inventory score 32 points) may have affected the levels of physical activity achieved. Limited information was available on the intensity of physical activity achieved, and this might be important because exercise may need to be performed at moderate-hard intensity for it to have a meaningful effect on depression.
To date there has been insufficient research on how the intensity and overall duration of exercise affects depression; future trials should include an objective measurement of physical activity. Any future trials should also, as in the TREAD trial, measure longer term outcomes and use standardised clinical interviews to diagnose depression to ensure the usefulness of the findings in a population with clinically diagnosed depression.
What should doctors advise their patients who present with depression? Within a clinical setting, for patients who are well managed on usual drugs or psychological treatments (or both), advice and support to be physically active does not seem to offer additional benefit and should not be given as standard. Indeed, recommending exercise to very depressed patients may worsen any thoughts of â€œfailureâ€ if they are unable to comply with the recommendation. However, positive results from trials in volunteers suggest that patients who are motivated to exercise and seek support to do so might benefit and should be supported in achieving this behavioral change