For patients with diabetes, the goal is tight control. The Diabetes Control and Complications Trial, the landmark diabetes study completed four years ago, concluded unequivocally that keeping a close reign on blood sugar can prevent or delay the kidney, eye and nerve complications that affect patients with diabetes. But for some with the disease, that goal is nearly impossible. Diabetics with depression have a very difficult time managing their blood sugar levels.Now, investigators at Washington University School of Medicine in St. Louis have found that treating clinical depression can help diabetic patients better control their blood sugar levels. Reporting in the May 22, 1997, issue of Psychosomatic Medicine, the researchers say the anti-depressant drug nortriptyline helps patients control their blood glucose, even though the drug itself tends to raise blood glucose levels. In depressed diabetics, treating depression more than made up for those increases in blood sugar.
"The drug had two opposing effects," explains Patrick J. Lustman, Ph.D., principal investigator and associate professor of psychiatry. "It improved depression significantly, but it worsened glucose control in patients who were not depressed. Yet, even in the face of this opposing effect, we found that as depression improved, glucose control did too."While depression affects about 5 percent of the general population at a given time, the rate is between 15 and 20 percent in patients with diabetes.
Lustman and colleagues studied 68 patients with diabetes. All had poor glucose control. Twenty-eight of them also were clinically depressed.Study participants were divided into four groups. Half of the patients with depression received the drug nortriptyline, a tricyclic anti-depressant. The rest received an inactive substance. Patients who were not depressed also were divided into nortriptyline and placebo groups. Then the patients were followed for eight weeks.
This was the first placebo-controlled study to establish that it is possible to treat depression in diabetic patients. "The drug therapy helped bring almost 60 percent of the depressed patients into remission," Lustman says. The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and in part by the Sandoz Corp., which provided the nortriptyline.
Depression has a negative influence on quality of life for anyone, but it can cause additional problems for patients with diabetes because it is closely associated with poor glucose control. Depression also is linked to poor compliance with diabetes treatment."There are several theories about why depression has such a negative effect on patients with diabetes," Lustman says. "Depressed patients may not comply with their treatment regimens, or perhaps depression may cause changes in neuroendocrine function, making blood sugar especially difficult to control."
Because depression makes it hard for a person to get anything done, it makes sense that the disorder might interfere with measuring blood glucose levels and exercising, watching one's diet or taking insulin. Therefore, treating depression could enable a diabetic patient to better manage diabetes. But Lustman says the study showed that better compliance alone did not explain the better blood sugar control.The researchers used electronic monitoring devices to determine whether the subjects took their medication. And they used memory glucometers to automatically record the dates and times that patients tested their blood glucose levels. They found that all of the participants followed their prescribed treatment regimens with little fluctuation during the eight weeks of the study.
In patients who were depressed and who were given nortriptyline, blood glucose levels improved along with psychiatric health. "Each one-point drop in the index that we use to measure depression correlated with a small reduction in blood sugar levels," Lustman says.He says the new study demonstrates that improvement in depression can translate into a clinically meaningful improvement in glucose control.
"Though the point-by-point change is small, the benefits could be substantial because many depressed patients drop more than 20 points in their depression index with effective treatment," he explains.Because the drug was administered to diabetic patients who were not depressed, it was possible to measure the direct effects of nortriptyline on glucose regulation. "We found that taking nortriptyline increased glucose levels in patients who took the drug but were not depressed," Lustman explains.
Other anti-depressants or non-drug interventions such as cognitive psychotherapy that do not have this opposing effect on glucose control may be more effective in diabetes management. Currently, Lustman is studying other treatment methods to see whether he can improve on his recent results.