Ray E. Clouse

ASSOCIATION OF DEPRESSION AND DIABETES COMPLICATIONS: A META-ANALYSIS

Objective The objective of this study was to examine the strength and consistency of the relationship between depression and diabetes complications in studies of type 1 and type 2 adult patients with diabetes. Method MEDLINE and PsycINFO databases were searched for articles examining depression and diabetes complications in type 1 and type 2 diabetes samples published between 1975 and 1999. Meta-analytic procedures were used. Studies were reviewed for diabetes type, sample size, statistical tests, and measures of diabetes complications and depression. Significance values, weighted effect sizes r, 95% confidence intervals (CI), and tests of homogeneity of variance were calculated for the overall sample (k = 27) and for subsets of interest. Results A total of 27 studies (total combined N = 5374) met the inclusion criteria. A significant association was found between depression and complications of diabetes (p < .00001, z = 5.94). A moderate and significant weighted effect size (r = 0.25; 95% CI: 0.22–0.28) was calculated for all studies reporting sufficient data (k = 22). Depression was significantly associated with a variety of diabetes complications (diabetic retinopathy, nephropathy, neuropathy, macrovascular complications, and sexual dysfunction). Effect sizes were in the small to moderate range (r = 0.17 to 0.32). Conclusions These findings demonstrate a significant and consistent association of diabetes complications and depressive symptoms. Prospective, longitudinal studies are needed to identify the pathways that mediate this association.

Prevalence of depression in adults with diabetes : an epidemiological evaluation

OBJECTIVE To determine the prevalence of depression in adult diabetic populations through a comprehensive literature review and to critically evaluate the methods and findings of such studies from an epidemiological perspective. RESEARCH DESIGN AND METHODS A systematic review of the scientific literature revealed a total of 20 studies, 14 of which had been conducted since 1988. Nine of the studies were controlled investigations, whereas the remaining 11 studies did not contain comparison groups. The studies included both treatment and community samples. RESULTS The range of the prevalence of current depression obtained from structured diagnostic interviews in diabetic samples was 8.5–27.3% ( = 14.0%) in controlled studies and 11.0–19.9% ( = 15.4%) in uncontrolled studies. These rates are at least three times the prevalence of major depressive disorder found in the general adult population of the U.S. Investigations using depression symptom scales corroborated these findings, as the range of clinically significant depression symptomatology in diabetic samples was 21.8–60.0% ( = 32.4%) in controlled studies and 10.0–28.0% ( = 19.6%) in uncontrolled studies. CONCLUSIONS An increased prevalence of depression in diabetes relative to the general population is highly suggested by the literature, but biases and methodological problems commonly encountered in prevalence studies may interfere with the strength of this conclusion. An increased prevalence of depression in diabetes relative to other somatic illnesses remains unproven. The pervasive impact of depression on quality of life and its potential negative effect on diabetes management warrant recognition and treatment of the affective disorder in diabetic individuals.

Cognitive Behavior Therapy for Depression in Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

Data from controlled studies [1-8] suggest that depression is more prevalent in diabetic patients than in the general U.S. population and that it is associated with poor glycemic control and decreased compliance with therapy [3, 5, 9-16]. Depression has also been associated with an increased risk for complications of diabetes, particularly cardiovascular disease and retinopathy [17-20]. The mechanisms of these associations are not fully understood, but it is plausible that alleviation of depression improves glycemic control and thereby decreases the risk for complications. Pharmacotherapy for depression may be poorly tolerated or may be insufficient to produce full remission in as many as 50% of diabetic patients with major depression [21-23]. The usefulness of nonpharmacologic approaches to the management of depression, such as psychotherapy, has not been systematically studied. Approximately two thirds of patients who have both diabetes and major depression do not receive specific antidepressant treatment, in part because their physicians tend to attribute their depression to poorly controlled or advancing diabetes [24, 25]. Therapy for these patients still largely centers on medical management, which may include emotional support and diabetes education; this approach is probably suboptimal. Our study was designed to determine the antidepressant efficacy of cognitive behavior therapy (CBT) added to supportive diabetes education. A secondary aim was to determine whether remission of depression is associated with improved glycemic control. Methods Patients Our study was advertised to primary care physicians working within the Washington University School of Medicine and BJC Healthcare System, St. Louis, Missouri, and it was publicized in various mass media advertisements. The study protocol was reviewed and approved by the Human Studies Committee of Washington University School of Medicine. Patients with type 2 diabetes mellitus who were 21 to 70 years of age were eligible for participation if they were able to answer questions, fill out study forms, and give informed consent. The diagnosis of type 2 diabetes was made according to the criteria developed by the American Diabetes Association [26] and was confirmed by a statement from the patients primary physician. Patients also had to meet the diagnostic criteria for major depression and had to have a score of at least 14 on the Beck Depression Inventory (BDI). Patients were excluded from participation if they had active suicidal ideation or a history of attempted suicide; had a history of panic disorder, bipolar depression, or any psychotic disorder; had a current substance abuse disorder; or were currently taking psychoactive medications. Assessment of Depression The presence of the major Axis I clinical syndromes was assessed by using the National Institute of Mental Health Diagnostic Interview Schedule (DIS) [27], and these syndromes were diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders [28]. The reliability and validity of the DIS in psychiatric and epidemiologic studies have been extensively reported [29]. Evidence also indicates that the DIS is sensitive and useful for patients with diabetes, in whom the somatic manifestations of the medical disease (such as fatigue, weakness, sleep disturbances, and sexual dysfunction) mimic the symptoms of a psychiatric disorder [30, 31]. Although the DIS is suitable for use by trained lay personnel, diagnostic evaluations in our study were done by a clinical social worker and a psychologist, both of whom had been trained in the use of the DIS by the instruments developers and the staff of the St. Louis site of the National Institute of Mental Health Epidemiologic Catchment Area Study [27, 32]. The severity of current symptoms of depression was measured by using the BDI [33]. This measure asks patients to provide a self-rating from 0 to 3 on each of 21 items; these ratings are added together to produce a total score. The BDI has been studied extensively and has been shown to be a reliable and valid measure of the severity of depression [34]. Depression manifests similarly on this instrument in diabetic and psychiatric patients, particularly with regard to the cognitive symptoms of depression [31]. Assessment of Diabetes Glycosylated hemoglobin (GHb) levels were measured to assess average glycemic control in the 120-day period before testing [35-37]. Total GHb levels were measured with the Pierce Glyco-Test (Pierce Chemical, Rockford, Illinois), an affinity assay that removes confounding by hemoglobin variants, such as hemoglobin F. The range of GHb levels for normal, nondiabetic persons in the Barnes-Jewish Hospital outpatient laboratory is 4.4% to 6.3%. In this laboratory, the between-run coefficients of variation for values greater than 6.6% are all 5% or less, the recommended standard [38]. The presence of complications of diabetes (neuropathy, retinopathy, and nephropathy) was determined by a physician-investigator on the basis of review of each patients medical history, current symptoms, physical examination results, and objective test results (which were obtained through review of clinical records). Assessment of Compliance Compliance with self-monitoring of blood glucose levels was determined by using electronic memory glucometers (LifeScan, Inc., Milpitas, California), which recorded the date, time, and result of blood glucose testing. Patients were instructed to test their blood glucose levels four times per day on two nonconsecutive days each week. Values for weekly compliance with blood glucose monitoring were computed by dividing the number of samples measured on the two test days by 8 (the number of tests requested) and multiplying the result by 100%. Study Design Patients were informed that depression in diabetes can be a cause or a consequence of poor glycemic control and that the study would determine whether focusing on the mental or the physical side of the problem was the most effective way to relieve depression. These concepts were familiar to most patients and were generally well accepted. No patients declined further evaluation because they were unwilling to accept random assignment. Patients who met the inclusion criteria and gave informed consent underwent a 1-week period of glucometer training and baseline assessment, after which they were randomly assigned to study groups. The randomization pattern was determined by a computer algorithm, and assignments were concealed in sealed envelopes. A secretary who was not otherwise involved with the study opened each patients envelope after the patient had completed the baseline assessment. During the 10-week treatment period, all patients participated in a diabetes education program by meeting in 1-hour, biweekly, individual sessions with a certified diabetes educator. A variety of diabetes self-care topics were covered in these sessions, and diet and exercise regimens were systematically reviewed and modified as needed. Patients continued to see their diabetologists during the trial, and these physicians were given GHb and glucometer data from our study to facilitate management. The diabetes education program was designed to control for the nonspecific effects of supportive attention as well as the potential influence of enhanced self-care and glycemic control on mood and ideation. Patients were randomly assigned to receive CBT or to receive no specific antidepressant treatment other than the diabetes education program. Patients in the CBT group received 1 hour of treatment weekly for 10 weeks from a licensed psychologist who had been the principal cognitive therapist in an early empirical trial of CBT [39]. Cognitive behavior therapy treats depression by using 1) behavioral strategies to re-involve patients in pleasurable social and physical activities; 2) problem-solving procedures to resolve stressful circumstances; and 3) cognitive techniques to identify distorted or maladaptive thought patterns and replace them with more accurate, adaptive, and useful views. Study outcomes were measured immediately after the end of the 10-week treatment period and at a follow-up evaluation 6 months later. At each evaluation, assessments of diabetic control and depression were made and scored independently of one another. The study personnel who monitored patient progress were not involved in treatment, and assessors were blinded to treatment assignments. No additional study protocol treatment was provided after the end of the 10-week treatment period. Patients who remained depressed at that point (BDI score 10) were referred to their primary physician for antidepressant medication or to a psychotherapist. Glycemic control and severity of depression were measured again at the 6-month follow-up visit, and patients were restudied at that time with an abbreviated psychiatric interview. Self-monitoring of blood glucose levels was not measured after the end of the 10-week treatment period. Statistical Analysis Differences in the demographic and clinical characteristics of patients receiving CBT and controls were determined in the intention-to-treat and completer samples by using the Fisher exact test for categorical data and the Student t-test for continuous data. The results of an intention-to-treat analysis of the depression outcomes are provided for the purpose of comparison [40, 41]. The analyses of study outcomes focused on the completer sample. Analyses of covariance (ANCOVAs) were used to determine the effects of treatment on symptoms of depression and glycemic control after treatment and at 6-month follow-up with beginning levels of the dependent measures (BDI score and GHb level) as the covariates. The post-treatment and follow-up BDI data were not normally distributed. Consequently, the scores were categorized and Fisher exact tests were used to analyze the data. We used ANCOVA for a secondary analysis afte

Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial.

Objective Depression is a prevalent and chronic condition in diabetes and is associated with poor glucose regulation and poor compliance with diabetes treatment. This investigation evaluated the effects of nortriptyline on depression and glycemic control to see whether depression in diabetes is treatable and whether restoring mental health contributes to improved medical outcome. Method: Sixty-eight diabetic patients with poor glycemic control, 28 of whom had active major depression (DSM-IIIR), completed a randomized, placebo-controlled, double-blind trial involving 8 weeks of treatment with nortriptyline targeted to therapeutic plasma levels (50-150 ng/ml). Depression improvement was determined with the Beck Depression Inventory; glucose control was measured by glycated hemoglobin levels. Compliance behavior was assessed using medication dispensing devices and glucometers equipped with electronic memory. Results: The reduction in depression symptoms was significantly greater in depressed patients treated with nortriptyline compared with those receiving placebo (-10.2 vs -5.8, p =.03). Nortriptyline was not statistically superior to placebo in reducing glycated hemoglobin of the depressed subjects (p =.5). However, path analysis indicated that the direct effect of nortriptyline was to worsen glycemic control whereas depression improvement had an independent beneficial effect on glycated hemoglobin. These findings were not explained by the relationships of nortriptyline treatment to weight change (r = -0.21, p =.31) or depression improvement to compliance with the protocol for self-monitoring of blood glucose (r = 0.01, p =.97). Conclusions: Major depression in diabetic patients can be effectively treated with nortriptyline at the expense of a direct hyperglycemic effect. Path analysis demonstrated a treatment-independent effect of depression improvement on glycemic control, suggesting that a more ideal antidepressant agent may both restore mental health and improve medical outcome.

Prevalence of anxiety in adults with diabetes: a systematic review.

BACKGROUND Anxiety is associated with decreased functioning and quality of life. It may have added importance in diabetes for its potential adverse effects on regimen adherence and glycemic control. OBJECTIVE To estimate the prevalence of clinically significant anxiety in adults with diabetes. RESEARCH DESIGN AND METHODS MEDLINE and PsycINFO databases and published reference lists were searched to identify studies that determined the prevalence of anxiety in diabetes from threshold scores on self-report measures or from diagnostic interviews. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. RESULTS Eighteen studies having a combined population (N) of 4076 (2584 diabetic subjects, 1492 controls) satisfied the inclusion criteria. Most did not adjust for the effects of moderator variables such as gender, and only one was community-based. Generalized anxiety disorder (GAD) was present in 14% of patients with diabetes. The subsyndromal presentation of anxiety disorder not otherwise specified and of elevated anxiety symptoms were found in 27% and 40%, respectively, of patients with diabetes. The prevalence of elevated symptoms was significantly higher in women compared to men (55.3% vs. 32.9%, P<.0001) and similar in patients with Type 1 vs. Type 2 diabetes (41.3% vs. 42.2%, P=.80). CONCLUSION GAD is present in 14% and elevated symptoms of anxiety in 40% of patients with diabetes who participate in clinical studies. Additional epidemiological studies are needed to determine the prevalence of anxiety in the broader population of persons with diabetes.

Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities. A double-blind, placebo-controlled trial.

Twenty-nine patients with esophageal symptoms and contraction abnormalities of the esophageal body completed a 6-wk, double-blind, placebo-controlled trial of trazodone (100-150 mg/day). Measures of esophageal and psychologic symptoms were completed at entry and at each follow-up visit. Esophageal manometry was repeated at the termination of the trial. Upon completion of the treatment, patients receiving trazodone (n = 15) reported a significantly greater global improvement than those receiving placebo (n = 14; p = 0.02). Although a variable clinical response was observed, the trazodone group had less residual distress over esophageal symptoms compared with the placebo group (59% +/- 9% vs. 108% +/- 19%, p = 0.03). Manometric changes observed during the course of the trial were not influenced by treatment nor by clinical response. Remarkable reductions in ratings of chest pain were reported by both treatment groups, emphasizing the importance of controlled trials when studying this patient population. We conclude that low-dose trazodone therapy can be of benefit in the management of symptomatic patients with esophageal contraction abnormalities. In addition, our findings support recent observations that manometric abnormalities characterizing this patient group may not be solely responsible for symptoms.

Tracheobronchial aspiration of gastric contents in critically ill tube-fed patients: Frequency, outcomes, and risk factors

Objectives:To describe the frequency of pepsin-positive tracheal secretions (a proxy for the aspiration of gastric contents), outcomes associated with aspiration (including a positive Clinical Pulmonary Infection Score [a proxy for pneumonia] and use of hospital resources), and risk factors associated with aspiration and pneumonia in a population of critically ill tube-fed patients. Design:Prospective descriptive study conducted over a 2-yr period. Setting:Five intensive care units in a university-affiliated medical center with level I trauma status. Patients:Each of the 360 adult patients participated for 4 days. Among the inclusion criteria were mechanical ventilation and tube feedings. An exclusion criterion was physician-diagnosed pneumonia at the time of enrollment. Intervention:None. Measurements and Major Results:Almost 6,000 tracheal secretions collected during routine suctioning were assayed for pepsin; of these, 31.3% were positive. At least one aspiration event was identified in 88.9% (n = 320) of the participants. The incidence of pneumonia (as determined by the Clinical Pulmonary Infection Score) increased from 24% on day 1 to 48% on day 4. Patients with pneumonia on day 4 had a significantly higher percentage of pepsin-positive tracheal secretions than did those without pneumonia (42.2% vs. 21.1%, respectively; p < .001). Length of stay in the intensive care unit and need for ventilator support were significantly greater for patients with pneumonia (p < .01). A low backrest elevation was a risk factor for aspiration (p = .024) and pneumonia (p = .018). Other risk factors for aspiration included vomiting (p = .007), gastric feedings (p = .009), a Glasgow Coma Scale score <9 (p = .021), and gastroesophageal reflux disease (p = .033). The most significant independent risk factors for pneumonia were aspiration (p < .001), use of paralytic agents (p = .002), and a high sedation level (p = .039). Conclusions:Aspiration of gastric contents is common in critically ill tube-fed patients and is a major risk factor for pneumonia. Furthermore, it leads to greater use of hospital resources. Modifiable risk factors for aspiration need to be addressed.

Depression in Adults with Diabetes

Major Depressive Disorder is present in 15% to 20% of patients with diabetes. The course of the illness is generally chronic; even after successful treatment depression will reoccur in as many as 80% of diabetic patients. Known to impair overall functioning and quality of life, depression has additional importance in diabetes because of its association with poor compliance with diabetes treatment, poor glycemic control, and an increased risk for micro- and macrovascular disease complications. Despite its relevance to the course of diabetes, depression is recognized and treated in approximately one third of cases. Criteria-based diagnostic systems (eg, DSM-IV) are sensitive and valid methods for detecting depression in diabetes even though unstable diabetes may produce some symptoms of depression. Brief paper-and-pencil tests like the Beck Depression Inventory can be used effectively in outpatient medical settings to screen for depression and help focus the health care team on patients in need of treatment. Data regarding the treatment of depression in diabetes are scant but promising and suggest that treatment is effective and has important positive effects on mood, glycemic control, and overall quality of life.

Psychiatric Illness and Contraction Abnormalities of the Esophagus

Over a six-month period 50 patients referred for clinical esophageal manometry were independently evaluated for psychiatric diagnoses to determine whether there was any association between psychiatric illness and esophageal motility disorders. The manometric studies were blindly classified according to findings in the esophageal body. Twenty-five patients were classified as having one or more of the following contraction abnormalities: an increase in mean wave amplitude, an increase in mean wave duration, an increased frequency of abnormal motor responses, or the presence of triple-peaked waves. Psychiatric diagnoses were made in 21 (84 per cent) of the 25 patients but in only 4 (31 per cent) of the 13 patients with normal manometric patterns (P less than 0.005) and 4 (33 per cent) of the 12 with other manometric abnormalities (P less than 0.01). The fact that psychiatric illness is associated with a specific cluster of esophageal contraction abnormalities may provide a basis for further investigation of the relation between emotional disturbances and disorders of gastrointestinal motility.

Screening for depression in diabetes using the Beck Depression Inventory.

Objective The purpose of this study was to determine the utility of the Beck Depression Inventory (BDI) as a screening tool for major depression in diabetes. Method One hundred seventy-two diabetic outpatients (insulin-dependent diabetes mellitus [IDDM] = 59, or non-insulin-dependent diabetes mellitus [NIDDM] = 113) being evaluated for a treatment trial were studied. BDI scores were calculated for the complete 21-item measure as well as for the cognitive (13 items) and somatic (eight items) symptom subgroups. The presence of depression was determined using the National Institute of Mental Health Diagnostic Interview Schedule in accordance with the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria. Receiver operating characteristic (ROC) analyses were used to evaluate the performance of the screening test in relation to the diagnostic standard. Results Depressed subjects were effectively discriminated from nondepressed subjects by using the full 21-item BDI, the cognitive items alone, or the somatic items alone (p <.001 for each comparison), although the cognitive items were more effective than the somatic items (p <.0005). BDI total scores between 12 and 14 inclusive displayed the best balance between sensitivity (0.90-0.82) and specificity (0.84-0.89), but a cutoff score > or = to16 for the entire 21-item measure exhibited the best balance between sensitivity and positive predictive value when prediction values were extrapolated to a diabetic population with a depression prevalence rate of 20%. This cutoff score would capture >70% of the patients diagnosed with major depression yet provide >70% certainly that a person screening positive actually has the psychiatric disorder. Conclusion The BDI is an effective screening test for major depression in diabetic patients. Prospective studies are needed to confirm the tests precise performance characteristics in the general clinical setting.