Sertraline-treated patients had greater improvement in A1C and systolic blood pressure levels than control patients, despite equivalent improvement in depression as measured by HAM-D. Thus, depression and pain scores () and QOL () improved significantly in patients receiving either sertraline or placebo, but there were no differences between the two groups. In contrast, although A1C levels fell significantly in both groups, the decrease in patients receiving sertraline was more than twofold greater than in those receiving the placebo, and this difference between groups was statistically significant. However, there was a very significant (P < 10−6) correlation of 0.45 between changes in depression and A1C levels in all of the subjects. A placebo effect to explain the significant fall in the control group would not be unexpected in this situation and may have been enhanced by the twice a month interaction with the study coordinator. The interaction with the study coordinator might also explain the similar improvements in depression, QOL, and pain scores between the two groups. These questionnaires were administered by the coordinator who often had to provide verbal explanations to the subjects about them. Perhaps the subjects did not want to “disappoint” her.
These robust positive effects of sertraline to significantly lower A1C levels in this study stand in contrast with most of the literature concerning treatment of depression in people with diabetes. In all of the randomized trials (11
), depression scores significantly improved. However, pharmacological treatment alone (11
) or psychological plus pharmacological treatment (15
) did not affect A1C levels. In one study (16
), patients were first treated in an open-label fashion with an antidepressant, and the 43% who responded were randomly assigned to continue either pharmacological treatment or to receive a placebo in a maintenance phase. Although recurrence of depression was significantly delayed by the active drug, the improvement in A1C levels during the open-label phase was maintained with no difference between the two groups during the maintenance phase. In a mildly depressed group of diabetic patients, A1C levels significantly decreased at 3 months, but there was no difference at 6 months between pharmacological and placebo treatment (18
). In a study evaluating cognitive behavior therapy, A1C levels were similar to those in a control group receiving no specific antidepressant therapy at the end of the 12-week treatment period but were significantly lower 6 months later (12
). However, these levels remained high in both groups (9.5% vs. 10.9%). Finally, in a randomized clinical trial in which depressed patients received a combination of pharmacological and psychological treatments compared with usual care, there was no difference in A1C levels when the entire groups were analyzed (15
). However, in the active treatment group, A1C levels fell significantly in those who had high depression scores compared with those with low scores. This difference was not found in the usual care group.
Conflicting results were seen in two open-label studies. In one, in which depression was treated with an antidepressant, A1C levels were significantly decreased in those whose depression improved but not in those who did not show a remission (17
). In the other one in which treatment was by group cognitive behavior therapy, depression significantly improved but there was no change in A1C levels (20
The PPVs for yes answers to question 1 only, to question 2 only, or to both on Whooley's questionnaire were 69, 67, and 84%, respectively. To the best of our knowledge, this is the first study to evaluate the PPVs of the responses to Whooley's questionnaire using an objective measure for the diagnosis of depression, the CDIS. These results suggest that this simple two-question screening tool could be an effective way to identify depressed patients in a busy office practice, especially if both questions were answered in the affirmative.
Because depression is significantly associated with treatment nonadherence (25
), it is likely that the improvement in A1C and systolic blood pressure levels in both groups was due to better adherence to the treatment recommendations of the nurses. One interpretation of these results is that increased contact with a sympathetic questioner (and listener) helps patients with depression, leading to better medication adherence, but pharmacological treatment of the underlying depression still yields an incremental benefit.
These results suggest an effective approach to the time constraints hindering primary care physicians caring for patients with poor glycemic control in whom depression is suspected, especially in low-income, minority populations. Whooley's screening questionnaire could be used liberally in those patients, and if results were positive (especially if both questions were answered in the affirmative), an antidepressant should be considered. These patients can be difficult to treat successfully, but, in this manner, both depression and uncontrolled diabetes and systolic blood pressure may be improved.