DURHAM, N.C. -- The Duke University Medical Center researchers who found evidence that exercise can be an effective treatment for major depression are embarking on a larger trial they believe will answer some of the remaining questions posed by their earlier results.
The new trial, which is being funded by a $3 million grant from the National Institute of Mental Health, is designed to further refine which depressed patients can benefit from exercise and determine why exercise appears to be effective. Additionally, the study will measure the effect of exercise on a phenomenon known as vascular depression, a form of depression that appears linked to actual abnormalities in blood vessels of the brain, and not brain chemical imbalances. The previous Duke studies, led by psychologist James Blumenthal, found that exercise was just as effective as the most common anti-depressive medication in reducing the symptoms of major depression.
"This new trial is intended to answer some of the ‘whys' posed by those original studies," Blumenthal explained. "We are very interested in evaluating behavioral, non-pharmacologic approaches to treating depression. Because up to one-third of depressed patients may not respond to drug therapy, and those who do take drugs may complain of side effects, it is important to find other approaches."
Over the next five years, the researchers plan to enroll 216 volunteers, half of whom will be assigned randomly to the drug arm of the trial and half to the exercise arm. The drug to be used is sertraline (trade name Zoloft), a member of a class of commonly used anti-depressants known as selective serotonin reuptake inhibitors, and the same drug used in the earlier trials.
Unlike the earlier trials, the new trial will have a placebo, or ineffective sugar pill, arm. Also unlike the earlier trials, the exercise arm will be divided as well -- half of the patients will do their exercises in the supportive atmosphere of the Duke Center for Living (CFL), while the other half will perform the same exercise regimens at home. Moderate exercise will be performed three times a week in both settings.
"One of the questions raised by previous studies was whether the supportive atmosphere of exercising in a group, with other similar patients and trainers, had any effect on relieving the depression," Blumenthal said. "At the completion of this trial, we should be better able to determine how much of the benefit was derived from exercise and how much, if any, came from the supportive atmosphere."
A new focus in this trial examines vascular depression, a form of the disorder that is not yet widely recognized, but is being actively studied by investigators at Duke and Cornell. "Vascular depression is a recently identified clinical type of depression," said Dr. Murali Doraiswamy, Duke psychiatrist and co-investigator of the trial. "We know, for example, that depression occurs at high rates in older patients who have other vascular diseases, such as heart disease, diabetes or stroke.
"We also know in the setting of these kinds of diseases that patients have compromised cerebrovascular function, apparently caused by tiny little strokes deep in the brain," he said. "There is a growing consensus that these changes may actually be mediating the high rates of depression in these patients."
Doraiswamy said that while depression is clearly associated with imbalances of key chemicals in the brain, there are likely many different causes behind these brain chemical changes. Duke studies have shown that up to one-third of the cases of depression in patients over the age of 65 may be due to this vascular form of the disease.
"We do not yet know the most optimal strategy to treat depression in such patients," Doraiswamy said. "Some data suggest that people with vascular lesions often do not respond as well to antidepressants.
"With this trial, we hope to determine if exercise improves blood flow in the brain and has a positive effect on relieving the depression," Doraiswamy continued. "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."
The treatment will last for four months, and patients will be followed up six months and one year later.
In order to be eligible for the trial, participants must be over the age of 54, sedentary and suffer from clinically diagnosed major depression. Symptoms include depressed mood or loss of interest or pleasure, combined with at least four of the following: sleep disturbances, weight loss, changes in appetite, psychomotor agitation, feelings of worthlessness or excessive guilt, impaired cognition or concentration, and recurrent thoughts of death.