decreased adherence to diabetes self-care behaviors, such as dietary recommendations, exercise behaviors, and oral hypoglycemic regimens (Ciechanowski 2000, Vickers 2006); decreased quality of life (Jacobson 1997a, Gaynes 2002); decreased social support (Sacco 2006); increased functional disability compared to nondiabetic patients with MDD (Egede 2004, Bruce 2005) as well as significant unemployment and work disability (Von Korff 2005); increased hospitalizations in children with T1D (Stewart 2005); and earlier mortality after adjusting for covariates (e.g., age, diabetes complications) (Katon 2005, Zhang 2005, Ismail 2007). Minor depression may also be associated with lower self-reported health status, cognitive limitations (e.g., confusion, memory loss, difficulty making decisions), and diabetes symptoms (Egede 2002b, Katon 2007, McCollum 2007), although additional evidence is needed to further elucidate this relationship.
Analyses of the economic impact of comorbid depression and diabetes have indicated that individuals with both disorders have higher ambulatory care use, greater prescription expenditures, and higher overall health care expenditures than patients with diabetes alone (Ciechanowski 2000, Egede 2002b, Finkelstein 2003, Jones 2004, Nichols 2007).
Depression as a Predictor of Diabetes
A bidirectional association has been observed for depression and diabetes in which depression has been found to increase the risk of the development of T2D in prospective longitudinal cohorts (Eaton 1996, Knol 2006, Engum 2007) and the presence of diabetes increases the risk of developing depression postdiagnosis (Anderson 2001, Ali 2006, Barnard 2006, Shaban 2006). Some studies have reported as much as a two-fold risk of subsequent T2D in the presence of MDD or moderate depressive symptoms (Eaton 1996, Engum 2007), whereas others report modest or nonsignificant risk estimates over similar periods after adjusting for covariates such as BMI and education (Carnethon 2003, Saydah 2003, Arroyo 2004, Golden 2004, Carnethon 2007). A meta-analysis of nine studies found a 37% increase in risk for T2D with a lifetime history of depressive symptoms (Knol 2006). Evidence from the Third National Health and Nutrition Examination Survey (NHANES III) suggests that a lifetime history of MDD among women under the age of 40 years increased the risk of metabolic syndrome, although additional studies are needed to confirm this finding (Kinder 2004).
Treatment Methods and Providers
Depression can be effectively treated in diabetes patients using traditional treatment modalities such as antidepressant medications, individual cognitive behavioral therapy (CBT), and problem-solving therapy (PST). Randomized placebo-controlled trials of tricyclic (e.g., nortriptyline) (Lustman 1997b) and selective serotonin reuptake inhibitor (SSRI) antidepressant medications (e.g., fluoxetine [Lustman 2000b], sertraline [Goodnick 1997], paroxetine [Paile-Hyvarinen 2003]) have been shown to be efficacious in treating depression. An uncontrolled randomized trial comparing fluoxetine and paroxetine showed comparable improvement in depression in a sample of patients with T2D and MDD (Gulseren 2005). Nortriptyline (25–50 mg q.d.) has been found to have a hyperglycemic effect on blood glucose control following treatment. Fluoxetine (40 mg q.d. maximum dose), sertraline (50 mg q.d. maximum dose), paroxetine (20 mg q.d.), and bupropion extended release (150–450 mg q.d.) (Lustman 2007) have been found to be associated with overall improvement in glycemic control and for BMI when bupropion was tested (Lustman 2007). Maintenance treatment using sertraline has been shown to be effective in extending depression remission compared to placebo (Lustman 2006), with sustained hypoglycemic effects observed for one year following depression remission in both placebo and sertraline treatment groups. In this study, younger adults (age <55 years) showed longer periods of symptom remission in the sertraline group compared with placebo and older adults (Williams 2007).
CBT has also been shown to effectively treat depression in patients with T2D in a randomized controlled trial compared to a diabetes education intervention (Lustman 1998). Improvements in A1C in the CBT group were observed at the 6-month follow-up evaluation and exceeded those of the control group.
Recent studies have demonstrated the efficacy of a collaborative care approach utilizing PST (Katon 2004c). In the Pathways study, T1D and T2D participants meeting criteria for MDD or dysthymia (persistent low-grade depressive mood lasting 2 or more years) from nine primary care health settings were randomized to either a case management intervention embedded within a primary care setting or usual care (UC). Patients receiving the case management intervention received a stepped-care approach utilizing education and support for antidepressant medication and/or PST delivered by trained clinical specialist nursing staff (Katon 2004c). Patients receiving the intervention showed greater improvements in adequate dosing of antidepressant medications, less severe depression, higher patient ratings of global improvement, and higher satisfaction with care over a 12-month follow-up period (Katon 2004c). Patients with two or more diabetes complications receiving the intervention showed greater improvements in depression outcomes at follow-up compared with the UC group. Patients with fewer than two diabetes complications showed comparable depression outcomes to the UC group (Kinder 2006). Patient attachment style was shown to be associated with depression treatment success using PST compared to UC (Ciechanowski 2006). Overall, no improvements in glycemic control or adherence to diabetes self-care behaviors were observed from baseline to 6- or 12-month follow-up evaluation (Katon 2004c, Lin 2006). A small decrease in BMI was observed and nonadherence to oral hypoglycemic agents increased over time in the intervention group (Lin 2006). Participants did not receive diabetes-specific education or adherence support for diabetes self-management that might have contributed to improvement in glycemic outcomes. This treatment approach has been shown to be a cost-effective means of providing treatment for co-occurring depression, with limited additional cost associated with the intervention and significant cost savings associated with non–mental health expenditures over time (Katon 2006, Simon 2007).
A variety of barriers to adequate treatment of depression in patients with diabetes have been identified. These include stigma associated with mental illness and patient perceptions of depressive symptoms as a form of weakness or an inevitable consequence of chronic illness (Egede 2002a); perceived discrimination in medical and mental health care resulting in racial and ethnic disparities in the use of depression treatment (Egede 2002a, de Groot 2006, Wagner 2007a); lack of screening and adequate diagnosis by primary care physicians (Katon 2004a); lack of dose adjustment of antidepressant medications by primary care providers (Katon 2004a); and lack of referrals to psychotherapy services in addition to antidepressant medication treatment (Katon 2004a). Patient satisfaction with the use of antidepressant medications and mental health providers has been shown to be favorable among those who have received depression treatment (Katon 2004c, de Groot 2006).
Recommendations for Future Research
Based on the available literature, a number of areas merit additional research attention to further define the etiology, course, outcomes, and treatment of comorbid depression and diabetes.
1. Little is known about the physiologic factors responsible for apparent increased rates of depression in T1D and T2D. Further research is needed to evaluate the neurochemical, hormonal, immune/inflammatory, and neurological contributors to depression in diabetes.
2. Although there is mounting evidence for increased prevalence of depression in T1D and T2D, the majority of studies have been cross-sectional and uncontrolled in design. Prospective, controlled studies are needed to better characterize the course and impact of clinical depression in diabetes as well as the unique contribution of depression on the development of metabolic syndrome and T2D. Clinical definitions and thresholds should be used to distinguish depression syndromes from short-term emotional states (e.g., adjustment to the diagnosis of diabetes or the development of a complication) and diabetes-related distress.
3. There is currently a paucity of literature addressing rates and correlates of depression among children with T2D and women with gestational diabetes.
4. Although there is strong evidence for the efficacy of one tricyclic antidepressant medication and four SSRI medications, more research is needed to characterize the efficacy of short- and long-term use and relationship to glycemic control of the full spectrum of SSRI and SNRI (serotonin and norepinephrine reuptake inhibitor) antidepressant medications in both adults and children with diabetes.
5. Additional research is needed to evaluate exercise as