Effect of modernized collaborative care for depression on depressive symptoms and cardiovascular disease risk biomarkers: eIMPACT randomized controlled trial

Abstract

Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, M_age = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges' g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results - 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93-7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers - i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, β-thromboglobulin, and platelet factor 4 (Hedges' gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention - which harnessed technology to maximize access and minimize resources - produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches. Trial Registration:ClinicalTrials.gov Identifier: NCT02458690.

Keywords: Autonomic dysfunction; Cardiovascular disease; Clinical trial; Collaborative care; Depression; Endothelial dysfunction; Internet interventions; Platelet activation; Systemic inflammation.

Figure 1.

Flowchart of Screening, Enrollment, Randomization, and Follow-Up for the eIMPACT Trial Note. Participants were screened and enrolled from August 13, 2015 to July 31, 2018. Data collection ended on July 31, 2020. ^aFor two of these participants, 12-month survey data were obtained. ^bFor all withdrawn by investigator (intervention: 3; usual care: 1), it was determined after randomization that the participant met an exclusion criterion.

Figure 2.

Mean Brachial Flow-Mediated Dilation (Endothelial Dysfunction; Panel A) and Hopkins Symptom Checklist-20 Scores (Depressive Symptoms; Panel B) at Pre-Treatment and Post-Treatment (12 Months) by Treatment Group Note. Values are from imputed datasets. Error bars represent 95% confidence intervals. P values are from analysis of covariance (ANCOVA) models using multiple imputation and adjusting for the stratification variables of age group and sex. Effect sizes (Hedges’ g) were computed from imputed Ms and SDs. Responder defined as a ≥50% reduction in SCL-20 score. FMD = flow-mediated dilation; SCL-20 = Hopkins Symptom Checklist-20.