TREAD carefully with your conclusions! Exercise to treat depression – is it effective?

Depression is one of the most prevalent mental disorders in the World and the global incidence is on the rise. It is already the leading cause of disability, and the fourth leading contributor to the global disease burden according to the World Health Organisation (WHO). WHO is predicting depression to reach second place in the rankings of disability-adjusted life years calculated for all ages and both genders. At least 121 million people are thought to be affected worldwide, with this figure likely being an underestimate.

Exercise has long been thought of as a positive treatment intervention for depression, and many healthcare practitioners recommend exercise as part of a treatment strategy. However, the publication of a new paper by Chalder and colleagues in the British Medical Journal at the start of this month has caused much controversy and debate amongst physicians and patients alike.

Chalder and colleagues reported the results of a UK-based multi-centre, two-armed parallel randomised controlled trial in primary care entitled the ‘TREAD’ study (TREAtment of Depression with physical activity).

The study participants were 361 adults aged between 18 and 69 who had consulted their primary care clinician with symptoms of depression. The intervention consisted of 3 face-to-face sessions and ten telephone calls with a trained physical activity facilitator over an 8 month period designed to offer individually-tailored support for patients to engage in physical activity, and both intervention and control groups were offered ‘usual care’ including antidepressant treatment.

The primary outcome measure was the Beck Depression Inventory score at 4 months follow-up, with secondary outcome measures of the same score at 8 and 12 months, and a self-reported measure of antidepressant use. Physical activity was measured by use of a self-reported 7-day recall diary in which individuals were requested to record 10 minute bouts of light, moderate, and vigorous physical activity, and these were subsequently converted to metabolic equivalents (METS) by multiplying by a factor thought appropriate to each level of activity. An attempt was made to check the validity of this method of data collection by comparison with accelerometry data which found a reasonable correlation between self-reported data and light-moderate physical activity, with less of a correlation at higher levels.

The group found no differences between the groups in Beck Depression Inventory scores at the four, eight or twelve month stage, and no evidence of a decrease in antidepressant use in the treatment group compared with the control group. They concluded that ‘The addition of a facilitated physical activity intervention to usual care did not improve depression outcome or reduce use of antidepressants compared with usual care alone.’

These findings sparked a number of media headlines in different sources including the Daily Telegraph newspaper, the BBC website, and the Guardian newspaper suggesting that exercise is not effective in the treatment of depression.This leap of faith in media reporting in pronouncing that exercise will not help to treat depression as a result of the findings of this trial is quite astonishing but perhaps not surprising.

The devil is, as ever, in the detail and there has been a vociferous response from clinicians and patients alike pointing out the many limitations of the study, including :

1) Questions about the accuracy of self-reported physical activity data ;

2) High drop-out rate during the trial (36.8% and 40.2% at 8 months) ;

3) Lack of a controlled physical activity intervention with doubts about the frequency, intensity, time and type of physical activity undertaken by individuals ;

4) Lack of recording of the exact nature of ‘physical activities’ that were performed by the intervention group including whether these were individual or group activities ;

5) Heterogeneity of possible diagnoses involving depressive symptomatology amongst the study groups (eg bipolar, unipolar, reactive, depressive personality disorder etc) ;

6) Lack of enough well-defined exclusion criteria ;

7) Debate about the suitability of the Beck Depression Inventory for monitoring a treatment response in patients with depression or with depressive symptomatology ;

8) Lack of availability of pre-study physiological parameters (eg VO2 max / Max HR etc) ;

9) Use of an arbitrarily-defined threshold for the ‘desired’ physical activity level ;

10) Lack of controlling for other possible bias and confounding factors (eg psychosocial issues such as alcohol use, unemployment, poverty, previous depressive illness etc).

There is a plethora of evidence for a positive treatment effect of exercise on depression. However, many studies to date have methodological limitations which makes it difficult to make firm conclusions about a treatment effect.

 A Cochrane review conducted by Mead and colleagues in 2010 included 25 relevant randomised controlled trials, many of which had methodological weaknesses, and concluded that exercise did seem to improve symptoms of depression but that the effect sizes were moderate and not statistically significant.

Regardless of the methodological limitations of the TREAD study, given the complicated nature of depression, together with the wider bio-psycho-social associated factors, perhaps a controlled trial to investigate the effects of physical activity on depression is not the correct approach to take, and certainly it looks like few conclusions can be taken from this trial and effectively translated into clinical practice.

If exercise is an effective intervention for some forms of depression then the optimum time, type, frequency, and intensity still remains unknown.

In addition, we are still unsure of the possible mechanisms for a treatment effect of physical activity and exercise on depression. These are complicated and may be divided into physiological and psychological mechanisms including:

1) Physiological – monoamine hypothesis, endorphin hypothesis, regulation of hypothalamo-pituitary axis ;

2) Psychological – distraction, self-efficacy, mastery and social interaction hypotheses.

There may, of course, be a combination of mechanisms involved.

CJSM would like to hear your thoughts about physical activity and exercise as a treatment for depression. In addition, we would like to hear your thoughts about study limitations in general, and issues related to the translation of knowledge into clinical practice.

In the meantime, here are a few blog links mentioning the TREAD study you might want to check out :

1) The lay scientist – Martin Robbins (UK)

2) The ‘Mind’ blog (UK)

3) Scientific American blog (US)

4) About.com depression blog (US)

5) Science Media Centre (NZ)

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References

1) Chalder M et al. 2012. Facilitated physical activity as a treatment for depressed adults: randomised controlled trial. BMJ 2012 344:e2758

2) Baxter H et al. 2010. Physical activity as a treatment for depression: the TREAD randomised trial protocol. Trials 11: 105

3) Mead GE, Morley W, Campbell P, Greig CA, McMurdo M, Lawlor DA. Exercise for depression. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD004366. DOI: 10.1002/14651858.CD004366.pub4.