Effect of a Digital Intervention on Depressive Symptoms in Patients With Comorbid Hypertension or Diabetes in Brazil and Peru: Two Randomized Clinical Trials

Abstract

Importance: Depression is a leading contributor to disease burden globally. Digital mental health interventions can address the treatment gap in low- and middle-income countries, but the effectiveness in these countries is unknown.

Objective: To investigate the effectiveness of a digital intervention in reducing depressive symptoms among people with diabetes and/or hypertension.

Design, setting, and participants: Participants with clinically significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score ≥10) who were being treated for hypertension and/or diabetes were enrolled in a cluster randomized clinical trial (RCT) at 20 sites in São Paulo, Brazil (N=880; from September 2016 to September 2017; final follow-up, April 2018), and in an individual-level RCT at 7 sites in Lima, Peru (N=432; from January 2017 to September 2017; final follow-up, March 2018).

Interventions: An 18-session, low-intensity, digital intervention was delivered over 6 weeks via a provided smartphone, based on behavioral activation principles, and supported by nurse assistants (n = 440 participants in 10 clusters in São Paulo; n = 217 participants in Lima) vs enhanced usual care (n = 440 participants in 10 clusters in São Paulo; n = 215 participants in Lima).

Main outcomes and measures: The primary outcome was a reduction of at least 50% from baseline in PHQ-9 scores (range, 0-27; higher score indicates more severe depression) at 3 months. Secondary outcomes included a reduction of at least 50% from baseline PHQ-9 scores at 6 months.

Results: Among 880 patients cluster randomized in Brazil (mean age, 56.0 years; 761 [86.5%] women) and 432 patients individually randomized in Peru (mean age, 59.7 years; 352 [81.5%] women), 807 (91.7%) in Brazil and 426 (98.6%) in Peru completed at least 1 follow-up assessment. The proportion of participants in São Paulo with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 40.7% (159/391 participants) in the digital intervention group vs 28.6% (114/399 participants) in the enhanced usual care group (difference, 12.1 percentage points [95% CI, 5.5 to 18.7]; adjusted odds ratio [OR], 1.6 [95% CI, 1.2 to 2.2]; P = .001). In Lima, the proportion of participants with a reduction in PHQ-9 score of at least 50% at 3-month follow-up was 52.7% (108/205 participants) in the digital intervention group vs 34.1% (70/205 participants) in the enhanced usual care group (difference, 18.6 percentage points [95% CI, 9.1 to 28.0]; adjusted OR, 2.1 [95% CI, 1.4 to 3.2]; P < .001). At 6-month follow-up, differences across groups were no longer statistically significant.

Conclusions and relevance: In 2 RCTs of patients with hypertension or diabetes and depressive symptoms in Brazil and Peru, a digital intervention delivered over a 6-week period significantly improved depressive symptoms at 3 months when compared with enhanced usual care. However, the magnitude of the effect was small in the trial from Brazil and the effects were not sustained at 6 months.

Trial registration: ClinicalTrials.gov: NCT02846662 (São Paulo) and NCT03026426 (Lima).

Conflict of interest statement

Conflict of Interest Disclosures: Dr Araya reported a pending patent for CONEMO (the digital intervention used in both studies). Dr Menezes reported receipt of grants from NIMH (U19MH098780) during the conduct of the study. Dr Brandt reported receipt of grants from NIMH (U19MH098780) during the conduct of the study. Dr Diez-Canseco reported receipt of grants from NIMH (U19MH098780) during the conduct of the study. Dr Hidalgo-Padilla reported receipt of grants from NIMH (U19MH098780) during the conduct of the study. Dr Cavero reported receipt of grants from NIMH (U19MH098780) during the conduct of the study. Dr Rocha reported receipt of grants from NIMH during the conduct of the study. Dr Scotton reported receipt of grants from NIMH during the conduct of the study. Dr Mohr reported receipt of grants from NIMH during the conduct of the study; personal fees from Otsuka Pharmaceuticals, from Apple Inc, Pear Therapeutics, and One Mind Foundation; and other from Adaptive Health Inc Equity Interest outside the submitted work. Dr Miranda reported receipt of grants from NIMH during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Flow of Participant Recruitment, Randomization, and Follow-up for the São Paulo, Brazil, Trial

aSome participants met more than 1 ineligibility criterion. bIndicates 44 participants in each unit. cNot all participants who remained enrolled in the trials attended follow-up assessments or completed all Patient Health Questionnaire-9 (PHQ-9) items. Numbers are included here to allow matching of the number of participants with tables presenting results. Eight participants in the intervention group and 11 participants in the enhanced usual care group who did not complete 3-month follow-up completed 6-month follow-up. dThe number of participants excluding those who withdrew consent or died (denominators) was 392 for the digital intervention group and 399 for the enhanced usual care group.

Figure 2.. Flow of Participant Recruitment, Randomization, and Follow-up for the Trial in Lima, Peru

aSome participants met more than 1 ineligibility criterion. bNot all participants who remained enrolled in the trials attended follow-up assessments or completed all Patient Health Questionnaire-9 (PHQ-9) items. Numbers are included here to allow matching of the number of participants with tables presenting results. Three participants in the intervention group and 6 participants in the enhanced usual care group who did not attend 3-month follow-up attended 6-month follow-up. cThe number of participants excluding those who withdrew consent or died (denominators) was 209 for the digital intervention group and 208 for the enhanced usual care group.

Figure 3.. PHQ-9 Scores at Baseline vs 3 Months and Violin Plots of PHQ-9 Scores at 3 Months in the Digital Intervention and Enhanced Usual Care Groups in São Paulo, Brazil, and Lima, Peru

In both scatterplots (left panels), the diagonal blue line divides participants who improved in Patient Health Questionnaire-9 (PHQ-9) scores at 3 months (below the line) from those who got worse (above the line). The diagonal brown line divides participants who achieved at least a 50% reduction from baseline PHQ-9 scores at 3-month follow-up (below the line) from those who did not achieve it (above the line), to illustrate the primary outcome. In the violin plots, the horizontal line in the box indicates the median, upper and lower ends of the boxes indicate the 25th and 75th quartiles, and the whiskers indicate the highest and lowest values within 1.5 times the interquartile range (IQR) of PHQ-9 scores. The wider gray shaded areas in the violin plots indicate a higher probability that members of the population will take on the given value; thinner areas indicate a lower probability. In São Paulo, the median score was 9 (IQR, 6-14) for the digital intervention group and 11 (IQR, 7-15) for the enhanced usual care group. In Lima, the median score was 6 (IQR, 2-12) in the digital intervention group and 10 (IQR, 6-14) in the enhanced usual care group.