Exercise training improves depressive symptoms in people with multiple sclerosis: Results of a meta-analysis

Highlights

• Current treatments are modestly effective for reducing depressive symptoms in MS.

• This meta-analysis indicates a small, yet significant effect of exercise training in MS.

• The effect was reliable across study and participant characteristics.

• Future exercise studies should include clinically depressed people with MS.

Abstract

Objective

There is a high prevalence, yet under-treatment of depressive disorder and symptoms by conventional therapy in people with multiple sclerosis (MS). We conducted a meta-analysis examining the overall effect of exercise training on depressive symptoms in MS.

Methods

We searched PubMed for randomized controlled trials (RCT) of exercise training and depression as an outcome in samples with MS. There were 13 RCTs that met inclusion criteria and yielded data for effect size (ES) generation (Cohen's d). An overall ES was calculated using a random effects model and expressed as Hedge's g.

Results

The weighted mean ES was small, but statistically significant (Hedge's g = 0.36, SE = 0.09, 95% CI = 0.18–0.54, z = 3.92, p < .001) indicating the exercise training resulted in an improvement in depressive symptoms compared to control. The overall effect was not heterogeneous (Q = 16.46, df = 12, p = 0.17, I² = 27.08); and post-hoc, exploratory analyses only identified depression symptom scale as a potential moderator variable (p = 0.04).

Conclusion

The cumulative evidence indicates that exercise training can yield a small, yet statistically significant and reliable reduction in depressive symptoms for people with MS.

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.