ReviewThe relationship of depression and diabetes: Pathophysiological and treatment implications
Introduction
Diabetes is a chronic disease that requires ongoing, multi-specialty medical care combined with patient self-management, family support, and education to prevent or delay end-organ morbidity and mortality (ADA, 2010). The prevalence of diabetes (which includes the four clinical classes of type 1, type 2, gestational, and diabetes due to other causes) was estimated at 2.8% world-wide in the year 2000 (Wild et al., 2004). Due to factors such as population aging and urbanization, 4.4% of the world's population is expected to have diabetes by 2030 (Wild et al., 2004). Within the United States, 17.5 million persons have been diagnosed with diabetes resulting in a total estimated annual cost of $174 billion (ADA, 2008). This includes $116 billion in excess medical expenditures and $58 billion in reduced national productivity (ADA, 2008). The actual national burden of diabetes is likely greater due to the social cost of intangibles such as pain and suffering, care provided by unpaid caregivers, excess medical costs due to undiagnosed diabetes, and other diabetes-attributed health care costs (ADA, 2008).
Another relatively common and costly central nervous system syndrome, major depression, occurs in many patients with diabetes. During the past two decades, multiple studies reveal that not only are depressive symptoms a risk factor for the development of type 2 diabetes, but they are also associated with premature onset of diabetes complications. We conducted multiple MEDLINE searches using terms such as “diabetes,” “depression,” and “pathophysiology” for the period, 2000–2010. This article reviews studies examining the relationship between depression and diabetes, neurochemical underpinnings of the two disorders, and the diagnosis and treatment of depression associated with diabetes. We examine the validity of rating scales used to diagnose depression in diabetic patients and review the literature on psychotherapeutic and psychopharmacologic management for these patients. The challenges of optimal depression screening and treatment in primary care settings of diabetic patients are currently under close scrutiny, especially regarding their potential impact related to improvements in diabetes-related outcomes and decreased health care costs, be it “depression” or “diabetes” relevant.
Section snippets
Epidemiological studies of depression and diabetes
The prevalence of clinically significant elevations in depressive symptoms or the presence of major depressive disorder (MDD) has long been recognized to be higher among persons with diabetes compared to non-diabetic populations (Anderson et al., 2001). Table 1 displays studies documenting increased rates of depression in diabetic populations. In 2001, Anderson and colleagues performed a meta-analysis of twenty controlled, cross-sectional studies, each containing a non-diabetic comparison group
The negative impact of depression on patients with diabetes: poorer glycemic control and premature diabetes-related complications and mortality
Considerable evidence indicates that depression is associated with poor glycemic control (Lustman et al., 2000a). A meta-analytic review of the literature showed a small to moderate, consistent effect size of 0.17 [95% CI 0.13–0.21] (Lustman et al., 2000a). This effect size was similar in studies of type 1 or type 2 diabetes, and increased upon the implementation of standardized interviews and diagnostic criteria to assess depression (Lustman et al., 2000a). Depression is also strongly
Pathophysiology of depression and diabetes
The epidemic of type 2 diabetes in the United States was increasingly recognized during the “Decade of the Brain” (1990–2000). During the subsequent decade of 2000–2010, increased attention focused upon adverse metabolic and thrombovascular consequences of depression through certain biologic pathways. Relevant in this regard are the hypothalamic–pituitary–adrenal axis hyperactivity and mental stress-induced sympathomedullary activation in many patients with major depression, which can
Diagnosis of depression in patients with diabetes
There are multiple conceptual approaches to the diagnosis of major depression in medically ill patients, including the exclusive and inclusive approaches (McDaniel et al., 1995). The exclusive approach maximizes specificity by eliminating somatic symptoms such as anorexia and fatigue, which frequently are elements of medical disorders (McDaniel et al., 1995). The inclusive approach includes all depressive symptoms to diagnose major depressive disorder in the medically ill and maximizes
Treatment of depression in patients with diabetes
Lustman and colleagues at Washington University in St. Louis have performed the vast majority of the research on treatment of depression in diabetic populations. Table 5 lists the results of double-blind, randomized controlled trials examining the psychotherapeutic and psychopharmacological treatment of depression in patients with diabetes. A randomized, controlled trial was conducted to determine the efficacy of cognitive behavioral therapy (CBT) in the treatment of major depression in
Future directions in treatment of depression in patients with diabetes
Collaborative care, structured care involving a greater role for non-medical specialists to augment primary care, has emerged as a potentially effective intervention to improve quality of care and patient outcomes in patients with depression and medical illnesses such as diabetes (Gilbody et al., 2006). A cumulative meta-analysis (examining 37 randomized studies including 12,355 patients with depression receiving primary care) showed that depression outcomes among patients receiving
Conclusions
Two common disorders, depression and diabetes, are complex diseases with manifold genetic and environmental contributors to pathogenesis. There is clearly an increased prevalence of depression among diabetic patients. Depressive symptoms serve as a risk factor for the development of diabetes and have been shown to contribute to hyperglycemia, diabetic complications, functional disability and all-cause mortality among diabetic patients. Despite the fact that depression complicates medical
Financial disclosures
James K. Rustad M.D., has no financial disclosures to report.
Dominique L. Musselman, M.D., M.S., received grant support from the National Institute of Mental Health (NIMH), The DANA Foundation, and Forest Laboratories, Inc.
Charles B. Nemeroff, M.D., Ph.D., served on the Board of Directors of NovaDel Pharma and Mt. Cook Pharma. He served on the Scientific Advisory Board of AstraZeneca Pharmaceuticals, CeNeRx BioPharma, NovaDel Pharma, PharmaNeuroboost, the American Foundation for Suicide
Role of the funding source
Not applicable for this manuscript.
Contributors
With the exception of the three authors, there are no other contributors to this manuscript.
Acknowledgement
There are no acknowledgements for this manuscript.
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