Digital Health Readiness: Making Digital Health Care More Inclusive.

This paper proposes an approach to assess digital health readiness in clinical settings to understand how prepared, experienced, and equipped individual people are to participate in digital health activities. Existing digital health literacy and telehealth prediction tools exist but do not assess technological aptitude for particular tasks or incorporate available electronic health record data to improve efficiency and efficacy. As such, we propose a multidomain digital health readiness assessment that incorporates a person's stated goals and motivations for use of digital health, a focused digital health literacy assessment, passively collected data from the electronic health record, and a focused aptitude assessment for critical skills needed to achieve a person's goals. This combination of elements should allow for easy integration into clinical workflows and make the assessment as actionable as possible for health care providers and in-clinic digital health navigators. Digital health readiness profiles could be used to match individuals with support interventions to promote the use of digital tools like telehealth, mobile apps, and remote monitoring, especially for those who are motivated but do not have adequate experience. Moreover, while effective and holistic digital health readiness assessments could contribute to increased use and greater equity in digital health engagement, they must also be designed with inclusivity in mind to avoid worsening known disparities in digital health care.

Effect of depression treatment on health behaviors and cardiovascular risk factors in primary care patients with depression and elevated cardiovascular risk: data from the eIMPACT trial.

BACKGROUND: Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk. METHODS: Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange. RESULTS: The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39). CONCLUSIONS: Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02458690.

Psychosocial predictors of health behavior adherence in heart-failure patients with comorbid depression: a secondary analysis of the Hopeful Heart trial.

BACKGROUND: Depression affects 20-30% of individuals with heart failure (HF), and it is associated with worse health outcomes independent of disease severity. One potential explanation is the adverse impact of depression on HF patients' adherence to the health behaviors needed to self-manage their condition. The aim of this study is to identify characteristics associated with lower adherence in this population, which could help to recognize individuals at higher risk and eventually tailor health behavior interventions to their needs. METHODS: Using data from a randomized, controlled, collaborative care treatment trial in 629 patients with HF and comorbid depression, we performed mixed effects logistic regression analyses to examine the cross-sectional and prospective relationships between medical and psychosocial variables and health behavior adherence, including adherence to medications, a low-sodium diet, and physician appointments. RESULTS: In cross-sectional analyses, married marital status and higher physical health-related quality of life (HRQoL) were associated with greater overall adherence (compared to married, single Odds Ratio [OR] = 0.46, 95% Confidence Interval [CI] = 0.26-0.80; other OR = 0.60, CI = 0.38-0.94; p = .012. Physical HRQoL OR = 1.02, CI = 1.00-1.04, p = .047). Prospectively, greater levels of social support were associated with improved overall adherence one year later (OR = 1.04, 95% CI = 1.00-1.08, p = .037). Social support, HF symptom severity, race and ethnicity, and age were predictors of specific types of adherence. Neither depression nor optimism was significantly associated with adherence outcomes. CONCLUSIONS: These results provide important preliminary information about risk factors for poor adherence in patients with both HF and depression, which could, in turn, contribute to the development of interventions to promote adherence in this high-risk population. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02044211 ; registered 1/21/2014.

Electronic Health Record Population Health Management for Chronic Kidney Disease Care: A Cluster Randomized Clinical Trial.

Importance: Large gaps in clinical care in patients with chronic kidney disease (CKD) lead to poor outcomes. Objective: To compare the effectiveness of an electronic health record-based population health management intervention vs usual care for reducing CKD progression and improving evidence-based care in high-risk CKD. Design, Setting, and Participants: The Kidney Coordinated Health Management Partnership (Kidney CHAMP) was a pragmatic cluster randomized clinical trial conducted between May 2019 and July 2022 in 101 primary care practices in Western Pennsylvania. It included patients aged 18 to 85 years with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 with high risk of CKD progression and no outpatient nephrology encounter within the previous 12 months. Interventions: Multifaceted intervention for CKD comanagement with primary care clinicians included a nephrology electronic consultation, pharmacist-led medication management, and CKD education for patients. The usual care group received CKD care from primary care clinicians as usual. Main Outcomes and Measures: The primary outcome was time to 40% or greater reduction in eGFR or end-stage kidney disease. Results: Among 1596 patients (754 intervention [47.2%]; 842 control [52.8%]) with a mean (SD) age of 74 (9) years, 928 (58%) were female, 127 (8%) were Black, 9 (0.6%) were Hispanic, and the mean (SD) estimated glomerular filtration rate was 36.8 (7.9) mL/min/1.73m2. Over a median follow-up of 17.0 months, there was no significant difference in rate of primary outcome between the 2 arms (adjusted hazard ratio, 0.96; 95% CI, 0.67-1.38; P = .82). Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker exposure was more frequent in intervention arm compared with the control group (rate ratio, 1.21; 95% CI, 1.02-1.43). There was no difference in the secondary outcomes of hypertension control and exposure to unsafe medications or adverse events between the arms. Several COVID-19-related issues contributed to null findings in the study. Conclusion and Relevance: In this study, among patients with moderate-risk to high-risk CKD, a multifaceted electronic health record-based population health management intervention resulted in more exposure days to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers but did not reduce risk of CKD progression or hypertension control vs usual care. Trial Registration: ClinicalTrials.gov Identifier: NCT03832595.

Characteristics and engagement among English-language online forums for addiction recovery available in the US.

In developing public resources for the Networks Enhancing Addiction Recovery - Forum Activity Roadmap (NEAR-FAR), we completed a systematic observational study of English-language online forums related to recovery from alcohol or other drug addiction in late 2021. Among 207 identified forums, the majority were classified as "general addiction" or alcohol-focused, though classifications related to other substances were common on websites hosting multiple forums. Commonly used social media platforms such as Reddit, Facebook, or Quora offered easily accessible venues for individuals seeking online support related to a variety of substances. Forums were related to established recovery programs such as 12-step and SMART Recovery as well as other nonprofit and for-profit recovery programs, and to community forums without formal recovery programming. Among 148 forums with any observed user activity, the median time between unique user engagements was 27 days (inter-quartile range: 2-74). Among 98 forums with past-month posting activity, we found a median of <10 posts per week (inter-quartile range: 1-78). This study compares three metrics of observed forum activity (posts per week, responses per post, time between unique user engagements) and operationalizes forum characteristics that may potentiate opportunities for enhanced engagement and social support in addiction recovery.

Predictors of Use and Drop Out From a Web-Based Cognitive Behavioral Therapy Program and Health Community for Depression and Anxiety in Primary Care Patients: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: A previously reported study examined the treatment of primary care patients with at least moderate severity depressive or anxiety symptoms via an evidence-based computerized cognitive behavioral therapy (CCBT) program (Beating the Blues) and an online health community (OHC) that included a moderated internet support group. The 2 treatment arms proved to be equally successful at 6-month follow-up. OBJECTIVE: Although highly promising, e-mental health treatment programs have encountered high rates of noninitiation, poor adherence, and discontinuation. Identifying ways to counter these tendencies is critical for their success. To further explore these issues, this study identified the primary care patient characteristics that increased the chances patients would not initiate the use of an intervention, (ie, not try it even once), initiate use, and go on to discontinue or continue to use an intervention. METHODS: The study had 3 arms: one received access to CCBT (n=301); another received CCBT plus OHC (n=302), which included a moderated internet support group; and the third received usual care (n=101). Participants in the 2 active intervention arms of the study were grouped together for analyses of CCBT use (n=603) because both arms had access to CCBT, and there were no differences in outcomes between the 2 arms. Analyses of OHC use were based on 302 participants who were randomized to that arm. RESULTS: Several baseline patient characteristics were associated with failure to initiate the use of CCBT, including having worse physical health (measured by the Short Form Health Survey Physical Components Score, P=.01), more interference from pain (by the Patient-Reported Outcomes Measurement Information System Pain Interference score, P=.048), less formal education (P=.02), and being African American or another US minority group (P=.006). Characteristics associated with failure to initiate use of the OHC were better mental health (by the Short Form Health Survey Mental Components Score, P=.04), lower use of the internet (P=.005), and less formal education (P=.001). Those who initiated the use of the CCBT program but went on to complete less of the program had less formal education (P=.01) and lower severity of anxiety symptoms (P=.03). CONCLUSIONS: This study found that several patient characteristics predicted whether a patient was likely to not initiate use or discontinue the use of CCBT or OHC. These findings have clear implications for actionable areas that can be targeted during initial and ongoing engagement activities designed to increase patient buy-in, as well as increase subsequent use and the resulting success of eHealth programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01482806; https://clinicaltrials.gov/study/NCT01482806.

Risk for Complicated Grief After the COVID-19 Death of a Marital Partner in Late Life.

OBJECTIVE: To identify 1) complicated grief symptom clusters among acutely-bereaved older adults who have lost a spouse to COVID-19 and 2) if spousal death due to COVID-19 increased risk of developing probable PGD METHODS: Eighty adults participating in a randomized controlled trial for depression prevention (mean age [± SD] = 70.4 [6.6]) completed the Inventory of Complicated Grief, every 3 months over a maximum of 15 months. Twenty-four percent (n = 19) of participants lost a spouse to COVID-19; 76% (n = 61) lost a spouse to other causes of death. Adjusted linear regression examined the associations between COVID-19 bereavement and six symptom clusters: yearning and preoccupation, anger and bitterness, shock and disbelief, estrangement from others, hallucinations, and behavior change. RESULTS: Compared to the non-COVID-19 group, the COVID-19 bereaved group reported greater shock and disbelief, hallucinations of the deceased, and estrangement from others. COVID-19 death was also associated with higher risk for probable prolonged grief disorder (PGD) at 12 months (odds ratio = 4.38, p = 0.027). CONCLUSIONS: Older adults who have lost a spouse to COVID-19 present with specific symptoms of distress and may eventually require clinical care for PGD.

Automated Messaging Program to Facilitate Systematic Home Blood Pressure Monitoring: Qualitative Analysis of Provider Interviews.

BACKGROUND: Hypertension is a leading cause of cardiovascular and kidney disease in the United States, yet blood pressure (BP) control at a population level is poor and worsening. Systematic home BP monitoring (HBPM) programs can lower BP, but programs supporting HBPM are not routinely used. The MyBP program deploys automated bidirectional text messaging for HBPM and disease self-management support. OBJECTIVE: We aim to produce a qualitative analysis of input from providers and staff regarding implementation of an innovative HBPM program in primary care practices. METHODS: Semistructured interviews (average length 31 minutes) were conducted with physicians (n=11), nurses, and medical assistants (n=6) from primary care settings. The interview assessed multiple constructs in the Consolidated Framework for Implementation Research domains of intervention characteristics, outer setting, inner setting, and characteristics of individuals. Interviews were transcribed verbatim and analyzed using inductive coding to organize meaningful excerpts and identify salient themes, followed by mapping to the updated Consolidated Framework for Implementation Research constructs. RESULTS: Health care providers reported that MyBP has good ease of use and was likely to engage patients in managing their high BP. They also felt that it would directly support systematic BP monitoring and habit formation in the convenience of the patient's home. This could increase health literacy and generate concrete feedback to raise the day-to-day salience of BP control. Providers expressed concern that the cost of BP devices remains an encumbrance. Some patients were felt to have overriding social or emotional barriers, or lack the needed technical skills to interact with the program, use good measurement technique, and input readings accurately. With respect to effects on their medical practice, providers felt MyBP would improve the accuracy and frequency of HBPM data, and thereby improve diagnosis and treatment management. The program may positively affect the patient-provider relationship by increasing rapport and bidirectional accountability. Providers appreciated receiving aggregated HBPM data to increase their own efficiency but also expressed concern about timely routing of incoming HBPM reports, lack of true integration with the electronic health record, and the need for a dedicated and trained staff member. CONCLUSIONS: In this qualitative analysis, health care providers perceived strong relative advantages of using MyBP to support patients. The identified barriers suggest the need for corrective implementation strategies to support providers in adopting the program into routine primary care practice, such as integration into the workflow and provider education. TRIAL REGISTRATION: ClinicalTrials.gov NCT03650166; https://tinyurl.com/bduwn6r4.

A chatbot-delivered intervention for optimizing social media use and reducing perceived isolation among rural-living LGBTQ+ youth: Development, acceptability, usability, satisfaction, and utility.

Background: Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) youth are at higher risk of isolation and depression than their heterosexual peers. Having access to tailored mental health resources is a documented concern for rural living LGBTQ+ youth. Social media provides access to connections to a broader and like-minded community of peers, but it also is a vehicle for negative interactions. We developed REALbot, an automated, social media-based educational intervention to improve social media efficacy, reduce perceived isolation, and bolster connections for rural living LGBTQ+ youth. This report presents data on the acceptability, feasibility, and utility of REALbot among its target audience of rural living LGBTQ+ youth. Methods: We conducted a week-long exploratory study with a single non-comparison group of 20 rural-living LGBTQ+ youth aged 14-19 recruited from social media to test our Facebook- and Instagram-delivered chatbot. We assessed pre- and post-test scores of social media self-efficacy, social isolation (4-item Patient-Reported Outcomes Measurement System - PROMIS), and depressive symptoms (Patient Health Questionnaire, Adolescent Version - PHQ-A). At post-test, we assessed acceptability (User Experience Questionnaire - UEQ-S), usability (Chatbot Usability Questionnaire -CUQ and Post-Study Satisfaction and Usability Questionnaire -PSSUQ), and satisfaction with the chatbot (Client Satisfaction Questionnaire - CSQ), along with two open-ended questions on 'likes' and 'dislikes' about the intervention. We compared pre- and post-test scores with standard univariate statistics. Means and standard deviations were calculated for usability, acceptability, and satisfaction. To analyze the responses to post-test open-end questions, we used a content analysis approach. Results: Acceptability of REALbot was high with UEQ-S 5.3 out of 7 (SD = 1.1) and received high usability scores with CUQ and PSSUQ (mean score (M) = 78.0, SD = 14.5 and M = 86.9, SD = 25.2, respectively), as well as high user satisfaction with CSQ (M = 24.9, SD = 5.4). Themes related to user 'likes' and 'dislikes' were organized in two main categories: usability and content provided. Participants were engaged with the chatbot, sending an average of 49.3 messages (SD = 43.6, median = 30). Pre-/post- changes in scores of perceived isolation, depressive symptoms and social media self-efficacy were not significant (p's > 0.08). Conclusion: REALbot deployment was found to be feasible and acceptable, with good usability and user satisfaction scores. Participants reported changes from pre- to post-test in most outcomes of interest and effect sizes were small to medium. Additional development and a formal evaluation of feasibility and engagement with behavioral targets is warranted.

Technological Innovations in Biobehavioral and Psychosomatic Medicine.

ABSTRACT: The role of technological innovations in health care has increased over the past years and will continue to improve the diagnosis, monitoring, and treatment of various physical and mental disorders. In biobehavioral and psychosomatic medicine, the use of technology has also increased in both research and clinical contexts. The articles in the current special issue of Psychosomatic Medicine focus on technological solutions that have been applied to patient-monitoring/assessment (health-related behaviors and vital functioning) and treatment (ehealth and mhealth interventions). Although such solutions are promising and considered acceptable by patients and health care providers, important barriers have also been identified regarding the implementation of these technological advances. Topics addressed in this issue cover the following themes: the use of biological and behavioral sensors that are linked to user smartphones, technological innovations in clinical conditions (asthma, alcohol-associated liver disease, and chronic pain), the use of virtual humans in clinical settings, digital mental health interventions, and the importance of reducing health disparities in the development and implementation of technological innovation. These topics are critically relevant to the field of biobehavioral and psychosomatic medicine and provide future directions for research and clinical practice.

Effects of Technology Assisted Stepped Collaborative Care Intervention to Improve Symptoms in Patients Undergoing Hemodialysis: The TACcare Randomized Clinical Trial.

Importance: Patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis often experience a high burden of debilitating symptoms for which effective treatment options are limited. Objective: To compare the effectiveness of a stepped collaborative care intervention vs attention control for reducing fatigue, pain, and depression among patients with ESKD undergoing long-term hemodialysis. Design, Setting, and Participants: Technology Assisted Stepped Collaborative Care (TACcare) was a parallel-group, single-blinded, randomized clinical trial of adult (≥18 years) patients undergoing long-term hemodialysis and experiencing clinically significant levels of fatigue, pain, and/or depression for which they were considering treatment. The trial took place in 2 US states (New Mexico and Pennsylvania) from March 1, 2018, to June 31, 2022. Data analyses were performed from July 1, 2022, to April 10, 2023. Interventions: The intervention group received 12 weekly sessions of cognitive behavioral therapy delivered via telehealth in the hemodialysis unit or patient home, and/or pharmacotherapy using a stepped approach in collaboration with dialysis and primary care teams. The attention control group received 6 telehealth sessions of health education. Main Outcomes and Measures: The coprimary outcomes were changes in fatigue (measured using the Functional Assessment of Chronic Illness Therapy Fatigue), average pain severity (Brief Pain Inventory), and/or depression (Beck Depression Inventory-II) scores at 3 months. Patients were followed up for 12 months to assess maintenance of intervention effects. Results: There were 160 participants (mean [SD] age, 58 [14] years; 72 [45%] women and 88 [55%] men; 21 [13%] American Indian, 45 [28%] Black, 28 [18%] Hispanic, and 83 [52%] White individuals) randomized, 83 to the intervention and 77 to the control group. In the intention-to-treat analyses, when compared with controls, patients in the intervention group experienced statistically and clinically significant reductions in fatigue (mean difference [md], 2.81; 95% CI, 0.86 to 4.75; P = .01) and pain severity (md, -0.96; 95% CI, -1.70 to -0.23; P = .02) at 3 months. These effects were sustained at 6 months (md, 3.73; 95% CI, 0.87 to 6.60; P = .03; and BPI, -1.49; 95% CI, -2.58 to -0.40; P = .02). Improvement in depression at 3 months was statistically significant but small (md -1.73; 95% CI, -3.18 to -0.28; P = .02). Adverse events were similar in both groups. Conclusions and Relevance: This randomized clinical trial found that a technology assisted stepped collaborative care intervention delivered during hemodialysis led to modest but clinically meaningful improvements in fatigue and pain at 3 months vs the control group, with effects sustained until 6 months. Trial Registration: ClinicalTrials.gov Identifier: NCT03440853.

Electronic health record based population health management to optimize care in CKD: Design of the Kidney Coordinated HeAlth Management Partnership (K-CHAMP) trial.

Primary care physicians (PCPs) provide the majority of medical care to patients with non-dialysis dependent CKD. However, PCPs report numerous limitations to providing expert CKD care, including poor patient education, inadequate diagnostic evaluation, suboptimal use of medications, and time limitations. The Kidney Coordinated HeAlth Management Partnership (Kidney CHAMP) trial is a cluster randomized controlled trial to evaluate the effectiveness of a novel centralized electronic health records (EHR)-delivered population health management (PHM) strategy for high-risk CKD patients on patient care, safety, and other outcomes of interest to patients, providers, and payors. Over a 42-month period, the trial will compare the effectiveness of a multifaceted intervention that combines early identification of high-risk patients, timely nephrology guidance, pharmacist-led medication management services, and CKD patient education to usual care and enroll 1650 high-risk CKD patients from 100 primary care practices. The primary outcome will be ≥40% decline in estimated glomerular filtration rate (eGFR) or end stage kidney disease. Key secondary outcomes will include blood pressure, renin-angiotensin aldosterone system inhibitors use, and exposure to potentially unsafe medications. If successful, our treatment approach could improve CKD care delivery and safety, resource allocation, and adoption of evidence-based CKD guideline-concordant care.

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

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, Mage = 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, ß-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.

Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).