Effect of a Collaborative Care Model on Depressive Symptoms and Glycated Hemoglobin, Blood Pressure, and Serum Cholesterol Among Patients With Depression and Diabetes in India: The INDEPENDENT Randomized Clinical Trial

Abstract

Importance: Mental health comorbidities are increasing worldwide and worsen outcomes for people with diabetes, especially when care is fragmented.

Objective: To assess whether collaborative care vs usual care lowers depressive symptoms and improves cardiometabolic indices among adults with diabetes and depression.

Design, setting, and participants: Parallel, open-label, pragmatic randomized clinical trial conducted at 4 socioeconomically diverse clinics in India that recruited patients with type 2 diabetes; a Patient Health Questionnaire-9 score of at least 10 (range, 0-27); and hemoglobin A1c (HbA1c) of at least 8%, systolic blood pressure (SBP) of at least 140 mm Hg, or low-density lipoprotein (LDL) cholesterol of at least 130 mg/dL. The first patient was enrolled on March 9, 2015, and the last was enrolled on May 31, 2016; the final follow-up visit was July 14, 2018.

Interventions: Patients randomized to the intervention group (n = 196) received 12 months of self-management support from nonphysician care coordinators, decision support electronic health records facilitating physician treatment adjustments, and specialist case reviews; they were followed up for an additional 12 months without intervention. Patients in the control group (n = 208) received usual care over 24 months.

Main outcomes and measures: The primary outcome was the between-group difference in the percentage of patients at 24 months who had at least a 50% reduction in Symptom Checklist Depression Scale (SCL-20) scores (range, 0-4; higher scores indicate worse symptoms) and a reduction of at least 0.5 percentage points in HbA1c, 5 mm Hg in SBP, or 10 mg/dL in LDL cholesterol. Prespecified secondary outcomes were percentage of patients at 12 and 24 months who met treatment targets (HbA1c <7.0%, SBP <130 mm Hg, LDL cholesterol <100 mg/dL [<70 mg/dL if prior cardiovascular disease]) or had improvements in individual outcomes (≥50% reduction in SCL-20 score, ≥0.5-percentage point reduction in HbA1c, ≥5-mm Hg reduction in SBP, ≥10-mg/dL reduction in LDL cholesterol); percentage of patients who met all HbA1c, SBP, and LDL cholesterol targets; and mean reductions in SCL-20 score, Patient Health Questionnaire-9 score, HbA1c, SBP, and LDL cholesterol.

Results: Among 404 patients randomized (mean [SD] age, 53 [8.6] years; 165 [40.8%] men), 378 (93.5%) completed the trial. A significantly greater percentage of patients in the intervention group vs the usual care group met the primary outcome (71.6% vs 57.4%; risk difference, 16.9% [95% CI, 8.5%-25.2%]). Of 16 prespecified secondary outcomes, there were no statistically significant between-group differences in improvements in 10 outcomes at 12 months and in 13 outcomes at 24 months. Serious adverse events in the intervention and usual care groups included cardiovascular events or hospitalizations (4 [2.0%] vs 7 [3.4%]), stroke (0 vs 3 [1.4%]), death (2 [1.0%] vs 7 [3.4%]), and severe hypoglycemia (8 [4.1%] vs 0).

Conclusions and relevance: Among patients with diabetes and depression in India, a 12-month collaborative care intervention, compared with usual care, resulted in statistically significant improvements in a composite measure of depressive symptoms and cardiometabolic indices at 24 months. Further research is needed to understand the generalizability of the findings to other low- and middle-income health care settings.

Trial registration: ClinicalTrials.gov Identifier: NCT02022111.

Figure 1.. Enrollment, Randomization, Follow-up, and Analysis of INDEPENDENT Study Patients

Patient Health Questionnaire-9 (PHQ-9) screening was offered to patients identified as having at least 1 poorly controlled cardiometabolic parameter through chart review. AIIMS indicates All India Institute of Medical Sciences; EDC, Endocrine and Diabetes Center; Diacon, Diacon Diabetes Hospital; MDRF, Madras Diabetes Research Foundation.

Figure 2.. Primary and Secondary Outcomes in a Study of the Effect of a Collaborative Care Model on Depressive Symptoms and Cardiometabolic Indices Among Patients With Depression and Diabetes in India

Primary outcome is the percentage of patients with ≥50% reduction in SCL-20 and at least 1 of the following: ≥0.5-percentage point reduction in HbA_1c, ≥5-mm Hg reduction in SBP, or ≥10-mg/dL reduction in LDL-C. Markers indicate unadjusted percentages of patients by treatment group and error bars indicate the 95% CIs. Estimates were generated with gaussian models using an identity link and a generalized estimating equation approach to account for correlation of observations within patients over time. Model effects are treatment group, time, treatment × time interaction, and site.

Figure 3.. Primary Outcome at 24 Months by Socioeconomic and Clinical Characteristics in a Study of the Effect of a Collaborative Care Model on Depressive Symptoms and Cardiometabolic Indices Among Patients With Depression and Diabetes in India

Risk differences were estimated with gaussian models using an identity link and a generalized estimating equation approach to account for correlation of observations within patients over time. Model effects are treatment group, time, treatment-by-time and treatment-by-subgroup interactions and site (except for subgroup analysis by site). AIIMS indicates All India Institute of Medical Sciences; EDC, Endocrine and Diabetes Center; Diacon, Diacon Diabetes Hospital; MDRF, Madras Diabetes Research Foundation; SCL-20, Symptoms Checklist Depression Scale.