Treatment of depression in diabetes: Impact on mood and medical outcome

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Abstract

Depression is prevalent as a co-morbid condition in diabetes. The efficacy of depression treatment with either pharmacological agents or psychotherapy has been demonstrated in the few available controlled trials. Depression has been associated with poor glycemic control and with accelerated rates of coronary heart disease in diabetic patients. Reported depression treatment trials demonstrate benefits of depression remission on glycemic control as well as mood and the potential for improvement in the course and outcome of diabetes. Because adverse effects of pharmacological agents on glycemic control have been observed, optimal therapies that improve both depression and measures of diabetes are still being sought. This review critically examines the efficacy of depression treatment in diabetes patients, the effects of depression treatment on the medical condition, and methodological issues important in the performance of treatment trials in the patient population.

Introduction

Depression severely impairs quality of life and all aspects of functioning in the diabetic patient [1], [2]. It aggravates the symptoms of medical illness, worsening the perception of diabetes, of its control and of its burden [3], [4], [5], [6], [7], [8]. Meta-analysis methods have demonstrated the relationship of depression with poor glycemic control and an increased risk for diabetes complications [9], [10]. The effects are not restricted to either principal type of diabetes, despite differences in pathogenesis of the disorders [9], [10]. These observations provide an impetus for specific attention to depression in diabetes, as diabetic complications, accelerated by poor metabolic control, are largely responsible for morbidity and mortality in this disorder. Depression consequently becomes one of the best predictors of hospitalization rate in diabetic patients [11].

The traditional argument, that depression results from the hardships imposed by diabetes and its complications, is not supported by observations from longitudinal studies or from studies dating depression and diabetes onsets in Type 2 diabetes [12], [13], [14], [15]. Although the onset of depression often follows the onset of diabetes in Type 1 diabetic patients [13], other observations demonstrate the importance of depression symptoms in either type once they appear. Forrest et al. [16] showed that depression symptoms were independent predictors of coronary heart disease (CHD) in Type 1 diabetics over 6 years of observation. Likewise, major depression accelerated the presentation of CHD in Type 1 and Type 2 diabetic women attending a diabetes registry, the 10-year risk being threefold greater in the depressed subset and independent of traditional risk factors [17]. In a separate study, depression independently predicted the progression of retinopathy in children with Type 1 diabetes when followed for a median of 10 years [18].

Evolving pathogenetic models incorporate information gleaned from studies of depression in nondiabetic samples. Depression may accelerate the presentation of CHD, the major source of morbidity in diabetes, through its effects on sympathetic activity, platelet activation and aggregation, and heart rate variability [19], [20], [21], [22], [23], [24], [25], [26]. More recently, a relationship between insulin resistance and depression has been demonstrated, a relationship that can be adjusted with depression treatment [27], [28], [29], [30], [31]. Insulin resistance is strongly associated with CHD risk, is the principal abnormality in Type 2 diabetes and, conceivably, could complicate the course of the Type 1 disorder. Depression-associated insulin resistance (DAIR) could account for the doubled risk of Type 2 diabetes associated with depression in prospective population-based studies in the US and Japan [14], [32]. In patients with established diabetes, DAIR may enhance the risk of CHD and provoke the range of diabetic complications associated with poor metabolic control (Fig. 1). When these biochemical–metabolic influences are combined with depression effects on adherence to medical treatment regimens, weight, physical activity, tobacco use and other cognitive–behavioral impairments, the potential negative burden of depression in diabetes is imposing [1], [33], [34], [35].

The hardships of diabetes management and its complications may well be the thrust behind the development of depression in some diabetic subjects, and hyperglycemia can promote or accentuate psychiatric symptoms [36], [37]. From the standpoint of the importance of depression detection and treatment, however, chicken–egg arguments have become passé. A sufficient body of literature favors exploring fully the effects of depression treatment on mood, glycemic control and complications in diabetic samples. Expectations remain that favorable outcomes could extend beyond depression relief and reversal of depression-impaired quality of life to reduced morbidity and mortality from the medical illness.

Section snippets

Efficacy of depression treatment in diabetic patients

Concerns were raised initially that efficacy of depression treatment in nondiabetic subjects could not be extrapolated to the diabetic population [34], even though antidepressants are effective across a wide range of medical illnesses [38]. Etiological differences for depression episodes may impose treatment resistance in the face of diabetes [34], [39]. Both 5-hydroxytryptamine sensitivity and hypothalamic–pituitary–adrenocortical (HPA) responsiveness are affected by hyperglycemia [37], [40],

Effect of depression treatment on the course of diabetes

Diabetes takes its toll through micro- and macrovascular complications that accrue over years following initial diabetes diagnosis. Depression may accelerate the rates [16], [17], [62], the acceleration accounting for some of the increased prevalence of diabetic complications in the depressed subset in cross-sectional studies [10]. Adverse depression effects may be more pronounced for some complications. CHD becomes manifested at more rapid rates in depressed diabetic subjects or in relation to

Methodological considerations in treatment trials

A variety of methodological considerations are specific to the study of depression treatment in diabetic patients and have been reviewed previously in detail [34]. Nonpharmacologic depression treatments may be favored by the majority of patients [80], [81], [82], [83], and some may be particularly useful in diabetes [84], [85]. Nevertheless, antidepressant medications remain the mainstay in practice because they are effective in face of most medical illnesses and are simple to prescribe [86],

Conclusions

Depression, a common comorbidity in diabetic patients, responds to treatment at rates approaching those in nondiabetic samples. Intervention is important not only for conventional effects on quality of life and daily functioning, but also for the potential gains toward improving the course and outcome of diabetes and its complications [100]. Both antidepressant medications and psychotherapy appear effective, although CBT may have a particularly promising role. Depression remission and sustained

Acknowledgements

This work was co-sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Mental Health, Bethesda, Maryland, January 2001.

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