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.

The prevalence of comorbid depression in adults with diabetes: a meta-analysis.

OBJECTIVE: To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. RESEARCH DESIGN AND METHODS: MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used chi(2) statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. RESULTS: A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8-2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). CONCLUSIONS: The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.

Depression and poor glycemic control: a meta-analytic review of the literature.

OBJECTIVE: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. RESEARCH DESIGN AND METHODS: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. RESULTS: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). CONCLUSIONS: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.

Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial.

OBJECTIVE: Depression is prevalent in patients with diabetes. It is associated with poor glycemic control and is linked to an increased risk for diabetic complications. In this study, we assessed the efficacy of fluoxetine for depression in patients with diabetes. RESEARCH DESIGN AND METHODS: Sixty patients with diabetes (type 1, n = 26; type 2, n = 34) and major depressive disorder entered an 8-week randomized placebo-controlled double-blind trial. Patients were given daily doses of fluoxetine (up to 40 mg/day). The Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAMD) were used to measure the severity of depression and to determine the percentage of patients who achieved substantial improvement or complete remission. GHb levels were obtained to monitor glycemic control. RESULTS: Reduction in depression symptoms was significantly greater in patients treated with fluoxetine compared with those receiving placebo (BDI, -14.0 vs. -8.8, P = 0.03; HAMD, -10.7 vs. -5.2, P = 0.01). The percentage of patients achieving a significant improvement in depression per the BDI was also higher in the fluoxetine group (66.7 vs. 37.0%, P = 0.03). Additionally, trends toward a greater rate of depression remission (48.1 vs. 25.9%, P = 0.09 per the HAMD) and greater reduction in GHb (-0.40 vs. -0.07%, P = 0.13) were observed in the fluoxetine group. CONCLUSIONS: Fluoxetine effectively reduces the severity of depression in diabetic patients. Our study demonstrated that after only 8 weeks, this treatment also produced a trend toward better glycemic control.

Predicting response to cognitive behavior therapy of depression in type 2 diabetes.

Little is known about which factors may adversely affect response to psychotherapy in diabetic patients with major depression. We studied the relationship of various demographic, diabetes, and depression characteristics to change in depression in 42 patients with type 2 diabetes who completed a randomized clinical trial of cognitive behavior therapy (CBT). Depression remitted in a significantly greater percentage of the patients treated with CBT than with the control intervention (85.0% vs 27.3%, p < 0.001). In the sample as a whole, nonremission of depression was associated with lower compliance with blood glucose monitoring, higher glycated hemoglobin (GHb) levels, higher weight, and a history of previous treatment for depression. In the group treated with CBT, the presence of diabetes complications and lower compliance with blood glucose monitoring were significant independent predictors of diminished response. These findings show that factors related to the medical illness, such as the presence of diabetes complications, may negatively influence the prognosis for recovery from depression. Specific coverage of these issues during psychotherapy may optimize the likelihood of treatment success in patients with diabetes.

Cognitive behavior therapy for depression in type 2 diabetes mellitus. A randomized, controlled trial.

BACKGROUND: Psychotherapy is the principal nonpharmacologic method for the management of depression, but its usefulness for depressed patients with diabetes remains unknown. OBJECTIVE: To assess the efficacy of cognitive behavior therapy (CBT) for depression in patients with diabetes. DESIGN: Randomized, controlled trial. SETTING: Referral-based academic medical center. PATIENTS: 51 patients with type 2 diabetes and major depression. INTERVENTION: Patients were assigned either to a group that received 10 weeks of individual CBT or to a control group that received no specific antidepressant treatment. All patients participated in a diabetes education program to control for the effects of supportive attention and the possible influence of enhanced diabetes control on mood. MEASUREMENTS: Degree of depression was measured by using the Beck Depression Inventory; glycemic control was measured by using glycosylated hemoglobin levels. Outcomes were assessed immediately after treatment and 6 months after treatment. RESULTS: The percentage of patients achieving remission of depression (Beck Depression Inventory score < or = 9) was greater in the CBT group than in the control group: posttreatment, 85.0% of patients in the CBT group (17 of 20) compared with 27.3% of controls (6 of 22) achieved remission (difference, 57.7 percentage points [95% CI, 33 to 82 percentage points]) (P < 0.001); at follow-up, 70.0% of patients in the CBT group (14 of 20) compared with 33.3% of controls (7 of 21) achieved remission (difference, 36.7 percentage points [CI, 9 to 65 percentage points]) (P = 0.03). Post-treatment glycosylated hemoglobin levels were not different in the two groups, but follow-up mean glycosylated hemoglobin levels were significantly better in the CBT group than in the control group (9.5% compared with 10.9%; P = 0.03). CONCLUSIONS: The combination of CBT and supportive diabetes education is an effective nonpharmacologic treatment for major depression in patients with type 2 diabetes. It may also be associated with improved glycemic control.

Tricyclic antidepressants for functional nausea and vomiting: clinical outcome in 37 patients.

Tricyclic antidepressants (TCAs) have been used successfully in the treatment of irritable bowel syndrome and unexplained chest pain. Little information is available regarding their use in other functional gastrointestinal disorders. Clinical charts were analyzed from 37 outpatients (mean age 45 +/- 2 years, 25 females/12 males) with chronic nausea and vomiting that could not be explained by any conventional organic disorder (mean duration of symptoms 28 +/- 8 months). Twenty-one (57%) had chronic persistent symptoms; 16 (43%) had intermittent relapsing symptoms; 13 (35%) also had pain as a dominant complaint. Each patient had been treated with TCAs specifically for the gastrointestinal symptoms (amitriptyline, desipramine, nortriptyline, doxepin, or imipramine), and the subject group was followed for 5.4 +/- 1.1 months. Response (at least moderate symptom reduction using a priori chart rating criteria) occurred in 31 patients (84%), and complete symptom remission occurred in 19 (51%)--in 41% with the first TCA trial. Dose at response averaged 50 mg/day, and outcome was unrelated to TCA used. Logistic regression analysis revealed that pain dominance interfered with remission (P = 0.03), but other clinical characteristics were not predictive of outcome. This uncontrolled clinical experience indicates that the open-label response rate of functional nausea and vomiting to low dosages of TCAs resembles that noted in irritable bowel syndrome. TCAs should be studied in controlled fashion for this and related dyspeptic syndromes, as the success of other treatments is limited.

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.

The course of major depression in diabetes.

The course of depression in patients with comorbid medical illness is poorly understood. We report a 5-year follow-up study of 25 diabetic patients who had participated in an 8-week depression treatment trial. When a patient completed the trial, primary physicians were informed of patient outcomes and advised to monitor for relapse and treat those with ongoing depression. At the 5-year reevaluation depression was assessed using DSM-III-R criteria, and a depression severity scale was formed that reflected the presence, severity, frequency, and duration of depression episodes as well as a global assessment of functioning. Recurrence or persistence of depression occurred in 23 (92%) of the patients with an average of 4.8 depression episodes over the 5-year follow-up period. The duration of the longest episode averaged 16 +/- 4 months. Reversion to major depression occurred frequently and rapidly also in the subset that remitted during the treatment trial: 58.3% were depressed again within the first year. At the time of the follow-up interview, major depression was evident in 16 (64%) of the subjects, and glycemic control was significantly worse in this group compared with those without depression (gHb: 13.3% +/- 2.6% vs 11.1% +/- 1.9%, P = 0.03). Severity of depression over follow-up was related to the presence of neuropathy at entry and to incomplete remission during the initial treatment trial. Nineteen patients (82.6% of those who relapsed) received additional courses of antidepressant therapy, but none was treated continuously for depression prophylaxis. In this diabetic sample, depression was a recurrent condition in the vast majority of cases, and initial treatment response did not confer lasting euthymia. Whether maintenance antidepressant medication would be useful in preventing depression recurrence and promoting better glycemic control in diabetes remains to be studied.

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 = 16 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% certainty 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 test's precise performance characteristics in the general clinical setting.

Screening for depression in pregnancy: characteristics of the Beck Depression Inventory.

OBJECTIVE: To determine the test characteristics of a self-report questionnaire, the Beck Depression Inventory, when used as a screening test for depression in a population of ambulatory pregnant women. METHODS: One hundred five pregnant women completed the Beck Depression Inventory and underwent a structured interview using the National Institute of Mental Health Diagnostic Interview Schedule-version III. Current depression was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-III-R. A receiver operating characteristic curve was constructed for the Beck Depression Inventory score as a predictor of current depression. A table of sensitivities, specificities, predictive values, and likelihood ratios was created for various cutoff values. RESULTS: For the 105 women enrolled, the median Beck Depression Inventory score was 8.0. Twelve women (11%) were diagnosed with current depression and had a median Beck Depression Inventory score of 25.5, compared with those without current depression, who had a median score of 8.0 (P = .001). The area under the receiver operating characteristic curve was 0.9940. Using a cutoff range of greater than 16, the sensitivity of the Beck Depression Inventory to detect current depression was 0.83, the specificity was 0.89, the positive predictive value was 0.50, and the negative predictive value was 0.98. CONCLUSIONS: The Beck Depression Inventory can serve as a rapid screening test for depression during pregnancy. A higher cutoff value is required for pregnant women than is customarily used outside of pregnancy.

Effects of alprazolam on glucose regulation in diabetes. Results of double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effects of alprazolam on glucose regulation in anxious and nonanxious patients with poor glycemic control and establish whether regulatory benefits are related to anxiolytic effects of the medication. RESEARCH DESIGN AND METHODS: Fifty-eight patients with poor glycemic control, 16 (27.6%) of whom had a symptomatic generalized anxiety disorder, were entered into a randomized, double-blind, placebo-controlled, 8-week trial using alprazolam (up to 2 mg/day) as the active agent. Generalized anxiety disorder was determined in accordance with Diagnostic and Statistical Manual of Mental Disorders criteria, and anxiety symptoms were measured using the Hopkins Symptom Checklist. Glycated hemoglobin levels were used to determine glucose regulation. Compliance behavior was assessed using glucometers and medication monitors equipped with electronic memory. RESULTS: A statistically significant reduction in glycated hemoglobin level was observed in patients treated with alprazolam compared with those receiving placebo (-1.1 vs. -0.3%, P = 0.04). This treatment effect was not a function of differences in compliance behaviors. Anxiety symptoms decreased in both alprazolam- and placebo-treated patients with generalized anxiety disorder, but reduction in glycated hemoglobin level was not dependent on alleviation of anxiety. CONCLUSIONS: A short course of alprazolam improved glucose regulation in patients with a history of poor diabetes control. This effect was not directly related to concomitant changes in anxiety. Alprazolam treatment of anxious patients with poorly controlled diabetes may result in decreased anxiety and improved glucose regulation through independent mechanisms.

Antidepressant therapy in 138 patients with irritable bowel syndrome: a five-year clinical experience.

BACKGROUND: Antidepressant agents may have a therapeutic role in functional gastroenterologic disorders, but controlled investigations in irritable bowel syndrome (IBS) have not provided satisfactory practice recommendations. To help with future study design, we reviewed a five-year clinical experience with antidepressant agents in out-patients with IBS. METHODS: Presenting features, treatment course, and clinical outcome were determined from a chart review of 138 patients attending a university-based gastroenterology practice. RESULTS: Patients were treated with up to five antidepressants in separate, consecutive trials if a satisfactory end-point had not been reached. Tricyclic antidepressants were utilized 130 times, newer antidepressants 39 times, and anxiolytic-antidepressants 47 times. Improvement and complete remission in bowel symptoms occurred in 89% and 61% of patients, respectively, during antidepressant therapy. Median dosages being prescribed when remission occurred were less than those conventionally used in clinical psychiatry (50 mg/day for several tricyclic antidepressants). Age, gender, symptom duration, and presence of psychological symptoms did not discriminate those who remitted from those who did not, whereas a pain predominant symptom pattern was more commonly associated with symptom remission (P < 0.05 comparing symptom patterns). Symptom remission was more likely during the first antidepressant treatment than with subsequent trials in the group with continued symptoms (P = 0.01), but nearly half of the patients with side effects or no benefit from the first agent who went on to subsequent trials remitted during treatment with an alternative antidepressant. CONCLUSIONS: The design of this retrospective review is not capable of determining the efficacy of antidepressants for IBS. Our observations in conjunction with other available data suggest that future trials should employ low daily dosages, carefully assess pain response, include patients with and without active psychiatric symptoms, and utilize a second agent for subjects intolerant or unresponsive to the first.

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% (mean = 14.0%) in controlled studies and 11.0-19.9% (mean = 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% (mean = 32.4%) in controlled studies and 10.0-28.0% (mean = 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.

Depression in adults with diabetes.

Depression in diabetes is a prevalent and chronic condition. The etiology is unknown but is probably complex; and biological, genetic, and psychological factors remain as potential contributors. Several neuroendocrine and neurotransmitter abnormalities common to both depression and diabetes have been identified, adding to etiological speculations. Pharmacotherapy of depression may improve both mood and glucose regulation in diabetes, although controlled studies of the efficacy of psychotherapy and pharmacotherapy for depression in diabetes are not yet available. Depression has potential interactions with diabetes on multiple levels and remains an important clinical focus independent of the medical disease.

Similarity of depression in diabetic and psychiatric patients.

Diabetic and psychiatric out-patients were studied to determine whether the symptom profile of depression was similar in medically ill and medically well subjects. The diagnosis of major depression was determined using psychiatric interviews and DSM-IIIR criteria. The 21-item Beck Depression Inventory (BDI) was used to characterize the prevalence and severity of depression symptoms, and the measure was divided into cognitive (13 symptoms) and somatic (eight symptoms) subsets. Seventeen (81%) of 21 symptoms (including 12/13 cognitive and 5/8 somatic symptoms) were not statistically different in prevalence or severity between the depressed diabetic patients (N = 41) and the depressed psychiatric patients (N = 68). Both of these depressed groups were significantly different from a nondepressed diabetic comparison group (N = 58) in the prevalence and severity of every BDI symptom except weight loss. These data show that the symptom profile of depression in diabetic patients (in particular the cognitive symptoms) is similar to that in depressed psychiatric patients and is readily differentiated from the symptom profile in nondepressed diabetic patients. Our observations support the diagnostic validity of the DSM-IIIR criteria for major depression in this medically-ill outpatient sample.

Major depression in coronary artery disease patients with vs. without a prior history of depression.

Major depression (MD) is common in patients with coronary artery disease (CAD). Some of these patients have a history of prior depressive episodes, whereas others experience their first episode around the same time that their CAD is diagnosed. The purpose of this study was to determine whether there are systematic differences between these two subgroups of depressed patients. Of 39 patients with recently diagnosed CAD who met DSM-III-R criteria for MD, 17 (44%) had a prior history of MD. This subgroup had a higher proportion of females (p less than 0.003), more severe depression (p less than 0.004), were marginally younger (p = 0.08), and had slightly less severe CAD (p = 0.07) compared with those with no prior history of MD. These results support the hypothesis that there may be two distinctive subtypes of MD in patients with CAD. Additional studies are needed to determine whether these subgroups differ with respect to course, treatment, and relationship to the coronary artery disease.

Underdiagnosis of depression in patients with coronary artery disease: the role of nonspecific symptoms.

OBJECTIVE: To determine whether the underdiagnosis of major depression (MD) in patients with coronary artery disease (CAD) may be explained by low specificity and mild severity of depressive symptoms in affected patients. METHOD: The Beck Depression Inventory (BDI) was used to assess depression symptoms in thirty-one patients with both CAD and MD, and eighty-three patients with CAD but without MD. RESULTS: Only ten (48%) of the symptoms were significantly more common in the MD than in the non-MD group, and nine symptoms were present in at least 20 percent of both groups. Of these nine nonspecific symptoms, only one (insomnia) was more severe in the MD patients than in the non-MD group (p < .006). When all twenty-one symptoms were rank ordered by frequency, the most common symptoms in the MD group were also the most common in the non-MD group (r = .91, p < .001). CONCLUSIONS: The symptoms of major depression were found to be relatively mild and nonspecific in patients with CAD. This may help to explain why depression is underdiagnosed in cardiac patients.