1000 Questions And Answers From Kumar Amp; Clark 39;s Clinical Medicine

[Adriene]

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The Treatment of Depression with physical activity (TREAD)[1] study is quite large and well designed. The results of the study got wide media coverage with the main message for the public to the effect that "Exercise Doesn't Treat Depression". This is quite unfortunate in my opinion since there are several aspects that have not been considered in the study design.

Depression is a common condition in Primary Care that typically has a relapsing course. This is important for General Practitioners since they see their patients over an extended period of time. It is equally important to them to cure a current episode as it is to prevent the possible next episode of depression. Effective interventions targeting relapse have the potential to dramatically reduce the point prevalence of the condition.

In this context one might consider the case of Mindfulness Based Cognitive Therapy (MBCT) which has shown to be effective in the relapse prevention of depression in patients who had more than two previous episodes.[2] MBCT which contains components of physical activity is however ineffective during active episodes of depression.[3]

This suggests the following considerations with regard to the present study. Firstly "patients were only eligible to be included in the study if they had a current diagnosis of ICD-10 depressive episode F32".[1] That implies that all patients in the free interval of their recurring condition were excluded from the study. Secondly, the authors state that they "excluded those who had failed to respond previously to antidepressants".[1] That probably means that many severe cases have been excluded.

To conclude the present study shows the ineffectiveness of physical activity in mild cases of depressive episodes while the effectiveness of physical activity for the relapse prevention in severe cases of depression remains an open question and a field for further research. A hasty generalisation that physical activity is ineffective for all cases of depression remains problematic.

The rapid responses to this article have been very interesting reading. I am in agreement with many of the points made by correspondents including that the conclusions drawn (by media and authors) seem to overreach the scope of the study. The authors' appear to do the equivalent of 'looking at the floor' as described by Nita Saini in her response about how people with depression start off walking.

This study looked at the effect of the intervention on the CIS-R and the BDI. The results were perhaps predictable but I am not sure the question posed was the one we want the answer to. This maybe one reason for the large number of responses and the media interest.

Sandy Whitelaw is the only correspondant so far to mention mental wellbeing but this is an area that is unexplored by the study which obviously was not set up to capture any potential wider benefits of exercise for people with depression.

Mental wellbeing is a dimension of feeling good and functioning well that is worthy of study in its own right and should not be seen solely as opposite to or the absence of depression (1). So, for instance, just because this intervention did not have a significant effect on BDI does not mean that it did not promote wellbeing which could be of value to the participants.

Exercise is identified as one of the 'five ways to wellbeing'(2) as discussed in the Foresight Report (3). It is an area where evidence is emerging and study is challenging but findings so far should not be dismissed. This is alluded to by other correspondants such as Carol Sinnott and Weber and Murray (11 June responses) who point out that there are all sorts of benefits of exercise; social interaction, structure to the day, taking responsibility etc.

Such factors are complex to look at but rather than continuing to confine ourselves to the foothills of measuring the negative it is high time clinicians, the research community and research funding awarding bodies rose to the challenge of research design that builds understanding of mental health that will have application for both medicine and wider society.

Regarding the TREAD (TREAtment of Depression with physical activity) study (1) in which the authors somewhat unexpectedly found negative results on a facilitated physical activity in patients with depression, the following issues should be seriously taken into account before getting to premature recommendation against exercise in this patient population in general. First of all, the severity of depression in this sample may not be generalisable to many patients with this chronic and frequently recurrent clinical condition. The study originally planned to recruit those with depression (as assessed with the International Classification of Diseases, 10th edition) not taking antidepressants or (presumably) taking them for less than eight consecutive weeks at the longest. Further, the study excluded those who had failed to respond previously to antidepressants.

Considering that antidepressants are seriously considered (or indeed frequently indicated) for those with moderate or severe depression and quite a few patients in the real-world actually fail to respond to a single antidepressant trial (2), the results pertain solely to milder forms of the illness for which nonspecific effects are not negligible (that may be exemplified as a well-known placebo effect in a drug comparative study). Further, while a goal of 1000 or more metabolic equivalent of task minutes per week might be too difficult to achieve for those with more severe illness who would have problematic fatigue and loss of goal-directed activities in the first place (note that the study originally aimed to the intensity of physical activity that is recommended for healthy adults), the percentage of those who were active beyond this threshold improved from 28% from baseline to 40-49% at follow-up periods in usual care group, suggesting a nonspecific effect that argues against any differentials between the two groups. Likewise, the use of antidepressants declined from 53 % at four months to 42% at 12 months in this group, which contrasts further from 59% to 35% in intervention group, respectively. While the dose of antidepressants is another problem, those with marked symptoms are unlikely to discontinue from antidepressant treatment within this timeline, again pointing to milder form of the illness.

Moreover, while this study utilized the Beck Depression Inventory (BDI) as the primary outcome measure, a lack of objective measures of depression is a limitation as well as assessments for subjective perspectives other than depression (as assessed with the BDI that gives us a clue on an aspect of the severity (3)) such as quality-of-life, well-being and self-esteem, or those for social functioning. Possible discrepancy of subjective versus objective evaluations is well possible (medicated in part by personality traits), and subjective improvements in mood may well translate into improvements in other subjective domains, or could ideally functioning in the end, the elements of which are all critically relevant for successful treatment of depression.

Many of the criticisms of previous studies that are discussed in the introduction, apply equally to the reported study. Although a relatively large study, some of the protocol decisions potentially contaminate the reported results, such as the fact that the 'usual care' group were still able to receive 'exercise by prescription', which if provided would dilute the between group differences based on exercise use. The intervention itself provided no direct exercise activity, but used 'motivational interviewing' to encourage participants to engage in physical activity. There was no direct measurement of activity undertaken, either by direct observation or by patient diary data, and therefore the reliability of data is open to interpretation. The use of a 7 day recall diary with 10 minute intervals is open to significant levels of recall bias. The reported results appear to be based more on the effect of contact with the activity coordinator, rather than effects from exercise/physical activity itself. In this way, the study does not in our view meet the requirements from a recent Cochrane review on this subject (2) as a 'methodologically robust trial'.

2. That due to the conflicting nature of the reported findings compared with the majority of other evidence, such attention may reduce the likelihood of people with depression seeking, and healthcare professionals offering, exercise as a possible treatment option, either formally or informally.

We are currently conducting a systematic review of the effects of exercise on depression. Early indications from this are overwhelmingly positive, showing that statistically significant clinical benefits are achieved through direct provision of exercise at preferred intensity (3), and that when structured exercise sessions are provided, this can benefit people with mild to moderate depression (4). The fact that the reported trial (1) does not provide a specific exercise programme, and does not monitor other than by self report (which is at best variable in interpretation), the intensity of the exercise, leads the reported results to be of questionable validity and reliability.

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