Depressed older adults with diabetes who were in practices randomized to the Intervention Condition were less likely to have died at the end of the 5-year follow-up interval than were depressed persons with diabetes in Usual Care after adjustment for baseline differences. Depressed patients without diabetes in the Intervention Condition were not at decreased risk compared to depressed patients without diabetes in Usual Care. The intervention attenuates the influence of diabetes on mortality risk among older adults with depression. We believe these findings support the integration of depression evaluation and treatment with diabetes management in primary care.
Before discussing our findings, the results must first be considered in the context of potential study limitations. First, we obtained our results from primary care sites in greater New York City, Philadelphia, and Pittsburgh, whose patients may not be representative of other primary care practices in the United States. However, the participating sites were diverse practices of varying size located in urban, suburban, and sparsely populated areas. Second, diabetes mellitus was based on self-report alone; however, relying on medical records may also be incomplete because many persons receive health care from providers in multiple systems. Studies have shown that self-reported data on diabetes as well as other chronic diseases is reliable (33
). Third, the question regarding diabetes might have included patients with impaired glucose tolerance who did not have diabetes. However, misclassification of some persons with impaired glucose tolerance as having diabetes would lead to a conservative bias towards the null (i.e., that there was no intervention effect for patients with diabetes on mortality). Fourth, the mortality reduction among depressed patients with diabetes randomized to the intervention may be due to factors other than the specific effects of a depression management program. For example, we have only a limited ability to address whether those patients with diabetes in the intervention practices were seen more frequently for reasons other than depression by their physicians; and similarly, we do not have information on specific diabetes outcomes such as hemoglobin A1c
. Fifth, misclassification of vital status was also a potential limitation. However, overall sensitivity of the NDI for ascertainment of vital status has generally been well over 90% in most studies (34
We selected patients with diabetes as a subgroup from the larger intervention trial (14
) realizing that we must proceed with caution about the inferences we make. Statisticians are wary of subgroup analyses, but clinicians must make decisions about individual patients (30
). At the same time, large-scale intervention studies carried out in primary care practice are limited, so we need to make the most of the data we have from intervention studies. Guided by published criteria for performing and reporting subgroup analyses (30
), we have identified a group, older persons with diabetes, for whom risk of death has been reported to be increased (10
). In addition, the link between diabetes, depression, and the outcome (mortality) may have common pathophysiologic mechanisms (38
). Finally, uncertainty persists about the influence of treatment of depression on outcomes for diabetes and other medical co-morbidity (8
). Consistent with recommendations regarding subgroup analyses, we reported the statistical significance of the interaction between intervention assignment and the condition of interest on the outcome (32
) and adjusted our estimates for potential imbalances in covariates across treatment groups (41
Despite some limitations, our study warrants attention because older depressed primary care patients with diabetes in practices implementing depression care management were significantly less likely to die over the course of a 5-year interval than were depressed patients with diabetes in usual care practices. To our knowledge, this is the first study to report on the relationship between diabetes and mortality in a depression intervention trial. A formal test of the interaction between intervention assignment and diabetes on the outcome of interest, all-cause mortality, was significant (32
). This suggests that persons with diabetes were more likely to benefit from the intervention than were persons without diabetes. Adjustment of the hazard ratio for imbalance in the distribution of baseline covariates assessed at baseline can be expected to yield estimates of the hazard closer to the true estimate of the treatment effect (40
). Because our sample was derived from primary health care, the public health significance of these findings is high.
The combination of clinical evaluation and monitoring, pharmacotherapy, and in some cases, interpersonal psychotherapy in the PROSPECT intervention appears to be effective in depressed patients with diabetes in reducing all-cause mortality risk. We realize that our study does not examine potential mechanisms underlying the relationship between the PROSPECT intervention and a decreased mortality risk among depressed patients with diabetes. Both physiologic factors such as increased inflammation (38
) and poor glucose regulation (3
) and behavioral processes such as poor adherence (3
) may link depression with increased mortality in patients with diabetes. The potential mediators between treatment assignment and outcomes for patients with diabetes deserve further study.
Our results add to the literature on clinical trial outcomes from treatment of depression in patients with diabetes. Specifically, the collaborative care model for depression, of which PROSPECT is one example, has been found to improve depression care and depression outcomes in patients with diabetes. The Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial found that depressed older adults with diabetes in a depression care management intervention had better depression outcomes at one year when compared to depressed older adults with diabetes in usual care although hemoglobin A1c
levels were unaffected by the intervention (9
). The authors point out that because patients had good glycemic control at baseline, power to detect small but clinically important improvements in glycemic control was limited. The Pathways Study randomized 329 patients with diabetes and comorbid major depression or dysthymia to depression care management or usual care and found that although depression outcomes were improved, no differences in hemoglobin A1c
levels were observed (8
). However, these authors also point out that the patients in the Pathways Study had good glycemic control at baseline.
In summary, our investigation adds new evidence to the literature on depression and diabetes, by examining whether the PROSPECT intervention influenced survival among depressed older primary care patients with diabetes. Specifically, these results indicate that a depression care management intervention can significantly reduce all-cause mortality among depressed patients with diabetes. These results should propel the development and dissemination of models of care that better integrate depression management for people with diabetes.