Improved mood, improved glycemic control in depressed patients with diabetes

Depression severity independently predicted long-term improvements in HbA1c levels.

Issue: April 2007

Changes in mood among patients with depression and diabetes predicted improvements in glycemic control, according to a new study. Changes in body composition also contributed to the glycemic control improvements over the short term.

Previous research has shown that depression increases the risk of developing type 2 diabetes, and can predict a more severe illness course. Although some studies have examined the effects of antidepressant medication on parameters of diabetes, they have done so without exploration of the underlying mechanisms.

“Currently it is not known whether antidepressant treatment-related improvements in HbA1c are mediated predominantly by weight change, especially during longer-term therapy or through weight-independent effects on factors influencing glucose regulation,” researchers wrote in Diabetes Care.

Patrick J. Lustman, PhD, a professor of psychiatry at the University of Washington in St. Louis, and colleagues examined the effects of the depression medication bupropion (Wellbutrin XL, GlaxoSmithKline) on HbA1c. They also examined whether the changes in HbA1c levels were related to changes in mood, diabetes self-care or anthropometrics.

Ten weeks of bupropion

The study consisted of an acute phase and a maintenance phase. During the acute phase, 93 patients with major depressive disorder received up to 10 weeks of treatment with bupropion. During the maintenance phase, those patients who achieved remission of depression received bupropion at the remission dose and were followed for up to 24 weeks or until their depression returned.

A total of 75 patients completed the acute phase of treatment. Those who did not complete the acute phase were more likely to be black (P=.007) and older at depression onset (P=.05). Of the 75 patients who did complete the acute phase, 63 (84%) satisfied the criteria for remission of depression after 10 weeks of treatment. Depression severity was measured using the Beck Depression Inventory (BDI), the Patient Health Questionnaire-9 (PHQ-9) and the Hamilton Depression Rating Scale (HDRS).

Among patients whose depression remitted, the severity of depression declined on all measures during the acute phase (BDI -18.1, PHQ-9 -6.8, HDRS -14.9; P<.01 for all). All 55 patients who subsequently completed the maintenance phase of the trial remained free of major depressive disorder.

Improvements in self-care

Diabetes self-care was monitored using the Summary of Diabetes Self-Care Activities scale. Raw scores on subscales measuring adherence to diet and exercise improved during the acute phase of the study and remained improved during patients’ depression-free interval of the maintenance phase.

“Anthropometric measures, except percent fat, declined significantly during the acute phase in the 75 patients who completed this phase of treatment,” the investigators wrote. “Similar changes were observed within the subsets of patients whose MDD remitted or did not remit during the acute phase.” Among those who completed the maintenance phase, changes from baseline were significant for weight, BMI and percent body fat, with a trend toward significance for total body fat mass.

In the total cohort, HbA1c decreased by 0.5% during the acute phase (P<.001), although this effect was entirely attributable to changes among patients whose MDD remitted. HbA1c levels remained lower during the depression-free interval of the maintenance period.

Multiple regression analyses were used to determine independent predictors of HbA1c during the acute phase and the maintenance phase. For the acute phase, baseline HbA1c and improvements in BDI (P=.046) and BMI (P=.013) predicted HbA1c. For the maintenance phase, however, only improvement in depression (P=.001) and baseline HbA1c remained significant predictors of HbA1c.

“It is encouraging that clinically important improvements in HbA1c can occur in the absence of large changes in anthropometrics,” the investigators wrote. The findings indicate that weight-independent physiological mechanisms may exist that have an effect on glycemic control; these could include changes to the hypothalamic- and limbic-hypothalamic pituitary-adrenal axes, hippocampal glucocorticoid receptors, the autonomic nervous system and immunoinflammatory processes, the researchers wrote.

“Our study affirms the importance of depression management in diabetic patients in its potential to improve glycemic control, even though the mechanisms involved are not fully understood,” the researchers wrote. “This advantage could lead to better outcomes, measured not only in quality of life but also in reduced or delayed onset of complications.”

For more information:

Lustman PJ, Williams MM, Sayuk GS, et al. Factors influencing glycemic control in type 2 diabetes during acute- and maintenance-phase treatment of major depressive disorder with bupropion. Diabetes Care. 2007;30:459-466.