Is Exercising an Rx for Depression?

Although current depression treatments are efficacious in a segment of the population with major depressive disorder (MDD), there is a clear need for alternative and augmentative treatment strategies.

Exercise is one such alternative treatment option. Previous research suggests four potential areas in which exercise may be beneficial for persons with depression.

1. Exercise as primary treatment

The utility of exercise in the treatment of MDD has been examined in several randomized controlled trials.

Dunn et al.1 compared two doses of aerobic exercise with an attention-control group (i.e. stretching).  Results of the 12-week trials indicated greater reductions in Hamilton Rating Scale for Depression in the high-dose exercise group compared to the low-dose exercise and attention control groups.

In another study, home-based and supervised exercise was compared to sertraline or pill placebo.2 Both exercise groups experience significant reductions in depressive symptoms compared to the placebo pill group.

Furthermore, there was no difference in treatment effects of the exercise groups compared to the sertraline. Results of these and other studies have been synthesized in several meta-analyses, all of which support the use of exercise in the treatment of MDD. 3-6 

2. Exercise as augmentation

To date, two RCTs have examined exercise as an augmentation treatment for non-remitted MDD. In one study, a 10-week exercise intervention resulted in significantly greater response compared to a control group in older adults who had received at least six weeks of antidepressant medications without a sustained response.7

Similarly, Trivedi et al.8 compared the efficacy of two doses of aerobic exercise as augmentation for non-remitted MDD. Following the 12-week intervention, the covariate adjusted remission rate for the high-dose group was 28.5% compared to 15.5% in the low-dose group (P=0.06).

3. Exercise to maintain treatment effects

Another challenge in the successful treatment of depression is maintaining treatment effects and preventing recurrent MDD episodes. No randomized trials have specifically aimed to examine exercise as a means to prevent relapse of depression. However, data from long-term follow-up studies of exercise suggest a potential benefit.

In a follow-up to the study described above comparing home-based and supervised exercise to sertraline or pill placebo, engagement in physical activity during the one-year follow-up period was a significant predictor of MDD remission. Furthermore, antidepressant medication used during the follow-up was not related to MDD remission.9

A similar analysis of a six-month follow-up to a study comparing exercise to: 1) sertraline and 2) a combination of exercise and sertraline.

Findings revealed participants in the exercise group had significantly lower relapse rates compared to subjects in the sertraline group and that exercise during the follow-up period reduced the risk for depression relapse.10

4. Exercise for improved health

Recent evidence suggests physical inactivity is a significant contributor to premature mortality.11

In fact, one study estimated the attributable fraction of all-cause deaths due to low cardiorespiratory fitness at 16% in men and 17% in women. By comparison, only hypertension similarly impacted mortality with 15% of deaths in men attributable to hypertension.

The proportion of deaths attributable to low fitness was greater than the combined attributable proportion of deaths from obesity, smoking, high cholesterol, and diabetes.12

The risks associated with inactivity are particularly important as persons with depression are at an increased risk of metabolic syndrome, diabetes mellitus, hypertension, cardiovascular disease, and ultimately, an increased risk of all-cause mortality.

Given that persons with depression are also less likely to engage in physical activity, targeted interventions in this population may have significant impact on the patient’s health.


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  2. Blumenthal JA, Babyak MA, Doraiswamy PM, et al. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. Sep-Oct 2007;69(7):587-596.
  3. Rethorst CD, Wipfli BM, Landers DM. The antidepressive effects of exercise: a meta-analysis of randomized trials. Sports Med. 2009;39(6):491-511.
  4. Lawlor DA, Hopker SW. The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ. Mar 31 2001;322(7289):763-767.
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  8. Trivedi MH, Greer TL, Church TS, et al. Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison. J Clin Psychiatry. 2011;72(5):677.
  9. Hoffman BM, Babyak MA, Craighead WE, et al. Exercise and pharmacotherapy in patients with major depression: one-year follow-up of the SMILE study. Psychosom. Med. Feb-Mar 2011;73(2):127-133.
  10. Babyak MA, Blumenthal JA, Herman S, et al. Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med. 2000;62:633-638.
  11. Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012;380(9838):219-229.
  12. Blair SN. Physical inactivity: the biggest public health problem of the 21st century. Br J Sports Med. Jan 2009;43(1):1-2.