Effectiveness of physical exercise in the treatment of depression in older adults as an alternative to antidepressant drugs in primary care

Currently, there is overwhelming evidence to show the health benefits of physical exercise [1]. The Global Burden of Disease study has classified sedentarism as the fifth leading cause of disease burden in Western Europe and as one of the main modifiable risk factors [2]. Yet, despite recommendations to promote exercise as a strategy capable of reducing the burden of chronic diseases, the frequency and intensity of physical activity in the population are rather disconcerting. Physical activity is currently ranked among the health determinants which exert most influence on morbidity and mortality. Moreover, exercise can partially reverse the effects of ageing in physiological functions and conserve functional reserve among older adults [3].

Depression is a common and disabling condition that affects over 120 million people worldwide [4] -at least one in five people during their lifetime- and has a significant impact on health status. While it is usually treated with antidepressants and/or psychological therapy, such treatments are not effective in all cases, and increasing attention has recently been given to some alternatives, and to aerobic exercise in particular [5].

Depressive disorders among the aged are a paradigm of geriatric care in terms of the importance of prevention, differences in pathogenesis, diagnostic and therapeutic complexity, associated high risk of failure, and severe impact on quality of life. Old age is the time of life when emotional fragility is accentuated. In addition to neurobiological changes in the brain, ageing inevitably entails an important loss over the years, not only in terms of individuals’ emotions, but also in terms of their physical condition and social status. Depression is the most common psychological disorder among people over the age of 65 years and affects approximately 15% of this age group [6].

Recent years have witnessed a dramatic rise in the prescription of antidepressant drugs, which has greatly increased health spending. Over half of the total cost of depression corresponds to direct costs, with those generated by antidepressant drugs becoming increasingly relevant. These drugs have undesirable effects, especially among the older population, with their use often being continued indefinitely and unnecessarily. It would therefore seem reasonable to test new therapeutic modalities which, a priori, would have fewer adverse effects and, most likely, a lower impact on health expenditure.

Among the reasons why exercise could improve depression is the belief that, on the one hand, it could act as a distraction from negative thoughts and that, on the other, it is possibly important to master new skills. In addition, social contact could form part of this mechanism. Physical activity can have physiological effects, such as bringing about changes in endorphin and monoamine levels, or decreases in the level of cortisol, the stress hormone, which may result in an improvement in patients’ mood [7]. Recent studies suggest that exercise stimulates the growth of new nerve cells and releases proteins, e.g., brain-derived neurotrophic factor, to improve the survival of nerve cells [8, 9]. Even so, a significant degree of uncertainty surrounds the effectiveness of exercise on depression [10, 11], mainly due to methodological considerations [12].

It should be stressed that older adults tend to be underrepresented in clinical trials in which both pharmacological and non-pharmacological measures for depressive disorders are assessed. Accordingly, and because these disorders present with special characteristics and a wide degree of clinical polymorphism among the elderly (difficulty in recognising the symptoms of depression, frequent somatic complaints, etc.), it would be of interest to carry out a clinical trial exclusively on adults aged over 65 years. This population group often presents with co-morbidities and, as a result, may be undergoing poly-pharmacy treatments. It is therefore important to demonstrate the effectiveness of non-pharmacological measures, such as physical exercise, in the case of depressive disorders.

The National Institute for Clinical Excellence (NICE) [13] conducted a systematic review on the likelihood of remission, reduction of symptoms and adherence to treatment among patients with depression who did and those who did not do exercise, and the different treatments available (pharmacological, psychotherapeutic, etc.), including a total of 25 clinical trials. Although the data which compared physical activity to antidepressant drugs indicated that there were no significant differences, the confidence intervals used by the studies were very wide, with the result that there was insufficient evidence to arrive at a conclusion. Overall, however, the studies suggested a benefit for physical activity -and more specifically for group-based physical activity- in the treatment of minor depression and mild-to-moderate major depression. In addition, physical activity has the advantage of contributing other health benefits, beyond a simple improvement in symptoms of depression [14].

The Guideline of the Institute for Clinical Systems Improvement [15] considers that physical activity could be a useful tool for ameliorating the symptoms of major depression. Another systematic review [16], in which only three studies with patients suffering from major depression were included, reported that physical exercise programmes significantly reduced the symptoms of depression, though the conclusions were limited by the heterogeneity and methodological shortcomings of the three studies evaluated.

A Cochrane review [17] analysed the relationship between physical exercise and depression. An attempt was made to answer the question of whether exercise might be more effective than drugs, psychological therapy or therapeutic abstention in reducing symptoms of depression. To this end, a total of 39 clinical trials of widely differing quality were jointly analysed. The results showed that: as compared to no treatment or a control group, exercise may have a moderately beneficial effect on symptoms of depression; and as compared to pharmacological treatment or psychological therapy, no differences were in evidence (conclusions based on very few studies). In only 4 trials [18–21], which covered a total of 298 patients, was physical exercise compared to pharmacological treatment (sertraline), and no statistically significant differences were observed, though only one of these studies specifically targeted persons over the age of 65 years [21] and included only 37 of such subjects. Furthermore, in none of these studies was follow-up longer than 16 weeks. This review was an update of a previous review [22] which suggested that exercise could reduce depressive symptoms.

New research studies are needed to further detail the type of exercise that could be beneficial for older adults with depression, analyse whether such exercise could be a therapeutic alternative to antidepressants or psychological treatment, and determine the related risks and costs. Prescribing physical exercise in the consulting room, as if it was a remedy for chronic disease, calls for knowledge about which exercise is the most suitable to the task, and the duration, frequency and intensity required.

Available evidence suggests that exercise may benefit depressed patients and be comparable to antidepressant treatment [23]. It seems reasonable, therefore, for exercise to be recommended to people with depressive symptoms and those who meet diagnostic criteria for depression [24]. As yet however, the best way of implementing this recommendation in clinical practice is not known (Sonnott, 2013). It has not been possible to provide patients with accurate information about how effective exercise can be, the relative benefits of aerobic, resistance or combined exercise, whether it is better to do such exercise individually or in a group, and the optimal duration of a session. Hence, to obtain a more accurate idea of the effect of exercise on depression among older adults, there is a need for new trials based on scientifically solid methodology, an adequate number of participants, and a sufficiently long follow-up.

The aim is to ascertain the non-inferiority of supervised physical exercise to antidepressant drug treatment in terms of reducing depressive symptoms among patients presenting with clinical criteria of a depressive episode (International Classification of Diseases -10th revision/ICD-10) diagnosed in primary care.

The results could be useful when it comes to finding a better and more effective approach to a health problem that is prevalent among older adults, and reducing the related disease burden on society as a whole. In terms of the number of patients and duration of follow-up, the proposed clinical trial is a project which easily surpasses the few studies on this subject that have been previously conducted on the elderly. Its aim is to provide scientific evidence on a therapeutic resource -physical exercise- which has undeniable health benefits and can be applied to certain health problems, such as depressive disorders, which are of great magnitude and considerable socio-economic relevance, and have a significant impact on the quality of life of older adults.

The project will make it possible to establish the type of specific physical exercise recommendations that are capable of reducing depressive symptoms among older people who meet clinical criteria for depressive disorders. Furthermore, the duration, frequency and intensity needed to ensure an efficacy similar to that of available drug treatments will be determined, thereby remedying some of the shortcomings present in the studies undertaken to date.

Should the hypothesis prove to be true, engaging in physical exercise could be regarded as a novel therapeutic resource in primary care for treating depression in older adults, and be incorporated into clinical practice guidelines along with the currently recommended pharmacological or psychotherapeutic treatments. This new therapeutic resource could have a favourable impact on the health and wellbeing of older adults, and serve to reduce health-care costs.

Among the obstacles to achieving the designated goals, mention should be made of the difficulty of conducting a trial with a high number of patients of advanced age, the need for adequate co-ordination among the different professionals, and the necessary adherence to the physical exercise programmes by the participants in order to obtain the expected benefits. The estimated sample size has been increased by 20% to offset the foreseeable loss of subjects across follow-up. Furthermore this is an open trial, seeing as what is being tested here is not a pharmacological intervention but a six-month-long physical activity programme, something that renders the use of masking techniques inviable. Even so, it is envisaged that all statistical analyses will be performed on a blinded basis, to ensure that the respective subjects’ group affiliations remain unknown to the assessor and thereby reduce any likelihood of the assessment of the effects of the intervention being biased.

In sum, it will enable the approach taken to depressive disorders in clinical practice to be changed, by offering a therapeutic alternative to existing treatments, unencumbered by the numerous adverse effects of antidepressant therapy and capable of reducing the frequent polymedication of older adults. In addition, the benefits of exercise can be extended to the cardiovascular area and musculoskeletal disorders, thus contributing decisively to more active ageing and a better overall level of health.