increase the risk for worsened glycemic control, earlier-onset diabetic retinopathy, and increased adolescent hospitalizations and emergency department visits (Kovacs 1995, Stewart 2005, Lawrence 2006).
Few studies have examined the naturalistic course of depression in adults with T1D and T2D. Depressive symptoms and affective disorders have been found to be highly persistent (e.g., 73–79% remain depressed) in prospective longitudinal investigations over 1–5 years follow-up (Lustman 1988, Peyrot 1999) with or without treatment. For example, a 5-year follow-up of patients enrolled in an 8-week antidepressant treatment trial found that 92% of patients experienced persistent or recurrent MDD, with 58% experiencing recurrence within 12 months of treatment (Lustman 1997c).
Impact of Depression on Diabetes and Psychosocial Outcomes
Depression has been found to be associated with worsened glycemic control and diabetes complications in diagnosed T1D and T2D samples. In a meta-analysis of 25 cross-sectional studies, small-to-medium effect sizes in the relationship between hyperglycemia and depressive symptoms were observed (Lustman 2000a). Recent cross-sectional studies have mirrored this finding among Hispanic adults (Gross 2004), children with T1D (Stewart 2005), and postmenopausal women with a lifetime history of MDD (Wagner 2007b). Prospective studies of changes in depressive symptoms have not shown depression to predict changes in glycemic control among ethnically diverse middle-age and older adults (Gary 2005, Trief 2006). Adherence to self-care behaviors does not appear to be a mediator between depressive symptoms and glycemic control among adults with T1D and T2D (Lustman 2005). A meta-analysis of 27 studies found medium effect sizes in the association between depression and worsened long-term diabetes complications (e.g., macrovascular disease, neuropathy, nephropathy, retinopathy, microvascular disease) in both T1D and T2D samples (de Groot 2001, Clouse 2003). Recent work examining the relationship of depression and diabetic neuropathy is consistent with these findings (Vileikyte 2005).
There is accumulating evidence for negative outcomes associated with comorbid depression including: 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
