Should doctors start prescribing exercise along with medication for major depression? or should they, in some instances, even prescribe exercise instead of medication? The answers aren’t in yet, but one thing is certain: The case for exercise as a weapon against depression is growing bit by bit.

To wit: A group of researchers at Duke University Medical Center in Durham, N.C., gave 156 study participants—all of whom were diagnosed with major depression—one of three depression treatments for four months: the antidepressant sertraline (Zoloft), exercise, or a combination of the two. Those in the exercise group attended three supervised classes a week in which they exercised on a treadmill or stationary bike at 70 percent to 85 percent of their maximum heart rate for 30 minutes. Those in the combination group performed the same exercise regimen in addition to taking sertraline.

At the end of the four-month treatment, all three groups exhibited similar results—significantly lower rates of depression. The investigators reported these results last year in the Archives of Internal Medicine. The researchers then continued to follow the study participants for another six months to see how they were faring, and these results, which were reported in the September/October Psychosomatic Medicine, also give exercise a largely favorable verdict as far as fighting depression is concerned.

For instance, a detailed analysis was made of the mental health status of the 83 patients who were in remission at the end of treatment. Remitted participants in the exercise group were more likely than remitted participants in the medication group to be partially or fully recovered at six months after treatment. In contrast, persons who had been in remission after receiving combination therapy were no more likely to be partially or fully recovered six months later than were persons who had been in remission after getting medication. In addition, only 8 percent of remitted patients in the exercise group subsequently relapsed, compared with 38 percent of remitted patients in the medication group, and 31 percent of remitted patients in the combination group.

"Our findings suggest that a modest exercise program is an effective, robust treatment for patients with major depression who are positively inclined to participate in it," said lead author James Blumenthal, Ph.D. He explained that he said "positively inclined" since study participants had volunteered for the study and therefore may have been especially motivated to exercise and to have had strong faith that exercise could help them.

Why remitted patients who had both exercised and taken medication did not fare as well as those who had simply exercised is not clear, Blumenthal admitted. However, he speculated, it is possible that the psychological benefits of overcoming depression solely through one’s own efforts might be greater than the psychological benefits that accrue from taking medication or from taking medication along with exercising.

The truth of the matter is, precious little is known about what happens in the brain when high hopes for the effects of exercise on depression encounter those physiological processes that underlie depression. In fact, little is known about how exercise per se alters the brain’s processes in order to banish the dark moods that constitute depression. And it is precisely to get a better idea of how exercise combats depression physiologically, and which patients can truly benefit from it, that the Duke University researchers will now be undertaking an even larger trial, with funds from the National Institute of Mental Health.

The trial will focus on vascular depression—depression that appears linked to abnormalities in blood vessels in the brain, not to brain chemical imbalances, and that may underlie the kind of depression seen in older persons who have vascular disease such as heart disease or stroke. The optimal strategy for treating this type of depression is not yet known, said Murali Doraiswamy, M.D., a Duke psychiatrist and coinvestigator in the Duke exercise-and-depression studies.

"With this trial," he explained, "we hope to determine whether exercise improves blood flow in the brain and has a positive effect on relieving the depression. Exercise would be a very attractive option for these patients. Since we know that exercise helps to control risk factors in cardiovascular disease, it seems logical to assume that it could be an ideal treatment for patients with vascular depression."