Exercise training improves depressive symptoms in people with multiple sclerosis: Results of a meta-analysis
Introduction
Multiple sclerosis (MS) is a disease of the central nervous system that often results in depressive disorder (i.e., clinical diagnosis and classification of depression based on an interview and diagnostic criteria) and depressive symptoms (i.e., symptoms such as sadness, hopelessness, and self-blame that are indicative of possible depressive disorder) [1], [2]. Indeed, an estimated 50% of patients with MS will develop a depressive disorder over the lifetime of the disease course [3]. One recent survey reported that approximately 47% of the 4178 respondents from the United Kingdom MS Registry had elevated depressive symptoms based on a Hospital Anxiety and Depression Scale (HADS) score of 8 or more [4]. That same study further reported an approximately 1 standard deviation difference in mean HADS depression scores between persons with MS and a United Kingdom population reference group [4]. This is problematic as depressive disorders and symptoms have been associated with cognitive impairment [5], reduced quality of life [6], and poor compliance with disease-modifying therapies [7] in MS. We further note that, upon detection, depression is often not treated adequately or treated at all [7]. Cochrane reviews provide evidence of only modest benefits for antidepressant medication [8] and cognitive behavior therapy (CBT) [9] in MS, but side effects of medications are often problematic and accessibility of therapists represents a major barrier for CBT. Based on a consensus statement released by the American Academy of Neurology [10], there is insufficient evidence regarding the efficacy of antidepressant treatment and/or individual and group therapies for managing depression in persons with MS. Such observations collectively underscore the importance of considering other treatment options for depression in MS.
Exercise training, defined as a planned, structured regimen of regular physical activity deliberately performed to improve one or more component of physical fitness (i.e., aerobic capacity or muscle strength and endurance) [11], represents a promising option for managing depressive disorder and symptoms in MS. This possibility is based, in part, on the broader body of research on exercise training for managing clinical depression and depressive symptoms in the non-MS population. For example, one meta-analysis documented the effect of supervised exercise training on depressive symptoms in healthy adults without clinical depression, and reported a mean effect size (ES) of 0.37 favoring exercise training compared with control [12]. Another meta-analysis examined the effect of exercise training on depression (both clinician diagnosed depressive disorder and depressive symptoms) in clinically depressed patients, and reported a mean ES of 0.61 favoring exercise training compared with control [13]. Such meta-analyses support exercise training for reducing depressive symptoms in both healthy adults without clinical depression and those with clinical depression.
There have been multiple randomized controlled trials (RCTs) of exercise training and depression in persons with MS. This body of research has recently been summarized in a literature review [14]. The researchers reported a total of 11 RCTs that examined the efficacy of exercise training on depressive symptoms as a secondary outcome measure in people with MS; there were no RCTs with clinician diagnosis of depressive disorders as an outcome. The researchers concluded that there was no overall distinct or clear pattern of results regarding the effect of exercise training on depression or depressive symptoms. This lack of a conclusion likely reflects that the 11 RCTs were neither designed nor powered for detecting a change in depressive symptoms with exercise training in persons with MS (i.e., the studies often had non-significant results, perhaps based on small samples, that yielded an uncertain conclusion based on vote counting of positive, negative, and null results). The lack of a conclusion based on a literature review can be overcome through a meta-analysis; this has not yet been done for depression in MS, but has been done for other outcomes wherein literature reviews were inconclusive (e.g. [15], [16]). Such a quantitative synthesis would provide a clearer picture regarding the overall existence and magnitude of a significant and possibly reliable effect of exercise training on depression in MS. The meta-analysis might further identify features of the studies (e.g., mode of exercise) and participants (e.g., disability level) that potentially moderate the effect of exercise on depressive symptoms. Both issues are important for the design of subsequent RCTs in this area.
We performed a meta-analysis examining the overall magnitude of effect for exercise training compared with control for improving depressive symptoms in people with MS. We further examined the features of the participants and studies as possible moderator variables. Such an analysis is important for informing clinical practice and the design of subsequent research. If exercise is an effective behavioral approach for reducing depressive symptoms, then it can be integrated into mood management interventions targeting people with MS. This is important considering the prevalence, impact, and modest efficacy of existing approaches [10] in managing clinical depression and depressive symptoms in MS. The resulting overall ES and any variation based on moderators could further be adopted for informing the design of future research, in particular for properly powering RCTs.
Section snippets
Methods
This meta-analysis was conducted consistent with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) framework [17], and a visual description of our step-by-step methods is provided in Fig. 1. We conducted a search of the electronic database PubMed using the key words exercise and multiple sclerosis for the articles published between 1960 and November 2013. Depression or depressive symptoms were not used as key words to avoid missing any potentially relevant studies during the
Results
The overall methodological quality of the studies along with the sample size and number, average, and the 95% CIsper study are provided in Table 1. Regarding methodological quality, 9 of the 13 studies received a score of 6 or higher on the PEDro scale; individual PEDro item scores for each study are provided in Table 2. The score of 6 has been previously determined as the cut-off point for a high quality study (i.e. Level I evidence) [59]. Table 3 provides the sample size, demographic and
Discussion
There have been meta-analyses demonstrating the favorable effect of exercise training on depression in healthy and clinically depressed persons without MS [12], [13], [62], [63]. We are further aware of a recent literature review indicating equivocal effects of exercise training on depression in MS [14]. To that end, we conducted the first meta-analysis of RCTs examining the effects of exercise training on depressive symptoms in people with MS. The evidence suggested that exercise training
Conflict of Interest
No authors have any conflict of interest to declare.
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