Physical Exercise As Treatment for Major Depression

September 4, 2012


"As a mental health professional, what should I know about physical exercise when I am treating my patients with major depression?"

Rakesh Jain, MD, MPH:

Even though mental health professionals are known as ‘mind’ clinicians, over the last decade published studies have shown that we are the quintessential mind-body clinician. Emerging data on the use of physical exercise to treat depression powerfully reinforces this very message—that depression is a mind-body disease and treating it requires a mind-body approach.

We have long advocated physical exercise for our patients, but primarily for its clear and convincing positive benefits on physical health. You may be surprised to hear that the data on exercise’s effects on mental health are very significant too! In fact, the data is so impressive that I am beginning to recommend it to every patient with a mood disorder that I treat.

Let’s first examine the data. Literally hundreds of pre-clinical studies on the effects of exercise on the brain have been conducted. Generally speaking they reveal that regular exercise in animal models have shown increases in the size of multiple organs critical in mood regulation, such as the hippocampus, as well as an increase in brain-derived neurotrophic factor in specific brain regions. If you are interested in this topic, two articles I recommend you consider reading are from Pereira et al. 1 and Russo-Neustadt et al. 2

There appears to be an additional benefit seen in animal studies—modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which as we know, is crucial in stress management. If you are interested in reading more on the HPA axis modulation in animal models, I recommend two specific articles from Fediuc et al. 3 and Droste et al. 4

There is a wealth of experimental and clinical data revealing positive effects on both the brain and mood in humans. Interestingly, exercise also appears to have a strong anti-inflammatory effect, which is an extra benefit to the individual with depression who exercises, as depression appears to have a large inflammatory component to it. Two studies worth reviewing to examine this experimental data in humans who exercise are from Pereira et al. 1 and Pedersen and Febbraio. 5

The clinical trials data are actually quite impressive. Let’s first examine a few individual studies, and then we will examine data from a meta-analysis.

One of the more impressive studies published relatively recently was conducted by Dunn et al. 6 Their data revealed that exercise as a therapy in patients with major depression was quite effective, but only if the patient exercised fairly rigorously and with regular frequency. Blumenthal and colleagues at Duke University published a study in 1999, 7 and then a follow-up study in 2007, 8 that compared the benefits of exercise with an established antidepressant. Exercise was nearly as effective as the antidepressant. Even more impressive, Blumenthal’s studies revealed that exercise was effective in mildly as well as severely depressed patients. It also revealed that both supervised and home-based exercise were effective as depression interventions.

Now, a meta-analysis by Mead and colleagues 9 looked at this data recently and it revealed some very interesting facts. It showed that exercise is effective in the young and old, male and female, and that regular exercise over weeks to months is more effective than infrequent exercise and both aerobic and resistance training are helpful. I highly recommend you read this article.

In summary, it’s time to start thinking about exercise as both a treatment for depression as well as an "add-on" recommendation for patients who are already on antidepressant medications. Exercise appears to have a positive biopsychosocial impact on our patients who suffer from depression.

Clearly, a challenge in clinical practice is how to get patient adherence with our exercise recommendations. You perhaps have faced this situation in your practice as well. It appears that the use of structured, supervised exercise is helpful, as is the use of exercise logs to motivate/monitor our patients with depression. I have attached a copy of an exercise log I use in my practice—you are welcome to download and use it, click here . Let our community of clinicians know how it worked for you!            

I invite your comments and questions. The learning experience will be richer if we communicate. I look forward to your postings on the topic of exercise and mood disorders.

Rakesh Jain, MD, MPH


  1. Pereira AC, Huddleston DE, Brickman AM, et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A. 2007;104(13):5638-5643.
  2. Russo-Neustadt AA, Alejandre H, Garcia C, et al. Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise. Neuropsychopharmacology. 2004;29(12):2189-2199.
  3. Fediuc S, Campbell JE, Riddell MC. Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats. J Appl Physiol. 2006;100(6):1867-1875.
  4. Droste SK, Gesing A, Ulbricht S, et al. Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary-adrenocortical axis. Endocrinology. 2003;144(7):3012-3023.
  5. Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88(4):1379-1406.
  6. Dunn AL, Trivedi MH, Kampert JB, et al. Exercise treatment for depression: efficacy and dose response. Am J Prev Med . 2005;28(1):1-8.
  7. Blumenthal JA, Babyak MA, Moore KA, et al. Effects of exercise training on older patients with major depression. Arch Intern Med . 1999;159(19):2349-2356.
  8. Blumenthal JA, Babyak MA, Doraiswamy PM, et al. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007;69(7):587-596.
  9. Mead GE, Morley W, Campbell P, et al. Exercise for depression. Cochrane Database Syst Rev. 2008;(4):CD004366.