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Exercise to Treat Depression, Backed by Biology

October 01, 2014

ORLANDO—Data on the neurobiology of exercise suggest that physical activity plays a key role in an integrative approach to treatment of depression and should regularly be included in the clinical arsenal. 

“Evidence shows that exercise changes brain structure and affects neurotransmitters, inflammation, and the autonomic nervous system. Exercise may have one of the widest ranges of effects that we see with any treatment,” said Rakesh Jain, MD, MPH, in a pre-conference presentation at the 27th Annual U.S. Psychiatric and Mental Health Congress. 

Exercise produces the commonly known “runner’s high” by releasing endogenous opioids, and it also augments endocannabinoid signaling, both of which are important to mood. 

Yet people do not need to be marathon runners to reap the physical benefits of exercise. In a notable study by Giraldo et al, sedentary women who were exposed to a single 45 to 60 minute exercise session showed enhanced phagocytosis ability in their white blood cells, a marker of improvement in the ability to fight off infections. 

Even 15 minutes on an exercise bicycle led to a positive impact on the function of the hypothalamic-pituitary-adrenal (HPA) axis, Dr. Jain noted in his research review. Furthermore, a study by Oertel-Knochel et al shows that exercise also improves cognition, especially speed of processing and working memory. 

Based on all these data, Dr. Jain feels confident that exercise is not simply a placebo. “The positive impact of exercise may not be all psychological. The biological component of exercise appears to be quite intense,” said Dr. Jain. 

How Much Is Enough? 

However, the discerning clinician will want to know the amount and type of exercise to prescribe for antidepressant benefits. 

A Cochrane database review analyzed 25 studies with this question in mind and concluded that patients must make a long-term commitment to exercise to reap its benefits. Another Cochrane review compared aerobic exercise, resistance training, and a mix of aerobic and resistance training. The review concluded that mixed exercise had the greatest effect size (1.47), followed closely by resistance training (1.34), and aerobic exercise (0.63). 

“Early in my career I would ask people to walk or runners to continue running,” said Dr. Jain. “I simply don’t remember asking my patients to do resistance training, but this review is changing my mind.” 

Dr. Jain also noted that intense exercise is most beneficial for patients. According to a study by Rethorst et al, moderate exercise had an effect size of 0.26 while intense exercise had an effect size of 0.78. 

“You may not want to start out with high intensity or ask your patients to start out with high intensity if they’ve been deconditioned for awhile. But the goal really ought to be to push the intensity of the interventions upwards,” said Dr. Jain. 

Instructions to patients should also include information about how long to continue an exercise program. Effect sizes for one or two weeks are not very good, though they increase from four to 9 weeks. The best effect sizes, said Dr. Jain, occur from 2.5 to four months of exercise but can fade if the patient stops the program. 

“My take-home message for my clinical practice is that I’m going to be recommending about an hour of exercise five times a week or more, and I’ll be asking for aerobic and resistance exercise with intensity,” said Dr. Jain. 

The above recommendation is not meant to apply across-the-board, as exercise may be a double-edged sword in bipolar disorder. When polled as part of a study, patients with bipolar disorder indicated that exercise brings structure to chaos, but clinicians must closely monitor the exercise habits of these patients. 

“If a patient is euthymic and exercising an average amount and then cut back that exercise, that could trigger him or her to drop into a depressive episode,” explained Dr. Jain. “It’s also important to remember that excessive exercise can precipitate a manic episode.” 

Guidelines Around the World 

Despite mounting evidence that exercise is a valid intervention for patients with depression, the United States lags behind other nations in terms of official recommendations. For example, in South Korea an independent body found that the efficacy of exercise is similar to that of antidepressant treatment or cognitive-behavioral therapy alone. As a result, exercise therapy is recommended for adult patients with mild or moderate depression. 

In other countries, including Australia, exercise is a covered form of therapy and patients can be referred to an exercise physiologist for depression, not just recovery from surgery. 

“It’s time for us in America to learn from the wisdom of our international colleagues,” said Dr. Jain. “But I do want to emphasize that all this great wisdom will go nowhere unless we monitor patients’ exercise.” 

To assist with monitoring and with convincing patients to continually exercise, Dr. Jain recommends using a scale that asks patients to chart their mood before and after exercise. Even if they miss a few times filling out the scale, they can still learn to recognize that exercise improves mood. 

“The data regarding exercise’s role in depression are very persuasive,” said Dr. Jain. “Is it time for all of us to adopt exercise in our clinical practices? It’s a question that only you can answer. But I certainly hope the answer is yes.” 

—Lauren LeBano 


1. Jain R. [pre-conference presentation]. July 15, 2014. Accessed September 4, 2014. 

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