Mediating Effects of Neural Targets on Depression, Weight, and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot Randomized Clinical Trial.

Background: Integrated treatments for comorbid depression (often with anxiety) and obesity are lacking; mechanisms are poorly investigated. Methods: In a mechanistic pilot trial, adults with body mass index ≥30 and Patient Health Questionnaire-9 scores ≥10 were randomized to usual care (n = 35) or an integrated behavioral intervention (n = 71). Changes at 6 months in body mass index and Depression Symptom Checklist-20 scores were co-primary outcomes, and Generalized Anxiety Disorder Scale-7 score was a secondary outcome. Changes at 2 months in the activation and functional connectivity of regions of interest in the negative affect circuit were primary neural targets, and secondary targets were in the cognitive control, default mode, and positive affect circuits. Results: Participants were 47.0 years (SD = 11.9 years), 76% women, 55% Black, and 20% Latino. Depression Symptom Checklist-20 (between-group difference, -0.3 [95% CI: -0.6 to -0.1]) and Generalized Anxiety Disorder Scale-7 (-2.9 [-4.7 to -1.1]) scores, but not body mass index, decreased significantly at 6 months in the intervention versus usual care groups. Only Generalized Anxiety Disorder Scale-7 score changes at 6 months significantly correlated with neural target changes at 2 months in the negative affect (anterior insula, subgenual/pregenual anterior cingulate cortex, amygdala) and cognitive control circuits (dorsal lateral prefrontal cortex, dorsal anterior cingulate cortex). Effects were medium to large (0.41-1.18 SDs). Neural target changes at 2 months in the cognitive control circuit only differed by treatment group. Effects were medium (0.58-0.79 SDs). Conclusions: Compared with usual care, the study intervention led to significantly improved depression but not weight loss, and the results on neural targets were null for both outcomes. The significant intervention effect on anxiety might be mediated through changes in the cognitive control circuit, but this warrants replication.

Can a Home-Based Collaborative Care Model Reduce Health Services Utilization for Older Medicaid Beneficiaries Living with Depression and Co-occurring Chronic Conditions? A Quasi-experimental Study.

Depression remains a major public health issue for older adults, increasing risk of costly health services utilization. While home-based collaborative care models (CCM) like PEARLS have been shown to effectively treat depression in low-income older adults living with multiple chronic conditions, their economic impact is unclear. We conducted a quasi-experimental study to estimate PEARLS effect on health service utilization among low-income older adults. Our secondary data analysis merged de-identified PEARLS program data (N = 1106), home and community-based services (HCBS) administrative data (N = 16,096), and Medicaid claims and encounters data (N = 164) from 2011 to 2016 in Washington State. We used nearest neighbor propensity matching to create a comparison group of social service recipients similar to PEARLS participants on key determinants of utilization guided by Andersen's Model. Primary outcomes were inpatient hospitalizations, emergency room (ER) visits, and nursing home days; secondary outcomes were long-term supports and services (LTSS), mortality, depression and health. We used an event study difference-in-difference (DID) approach to compare outcomes. Our final dataset included 164 older adults (74% female, 39% people of color, mean PHQ-9 12.2). One-year post-enrollment, PEARLS participants had statistically significant improvements in inpatient hospitalizations (69 fewer hospitalizations per 1000 member months, p = 0.02) and 37 fewer nursing home days (p < 0.01) than comparison group participants; there were no significant improvements in ER visits. PEARLS participants also experienced lower mortality. This study shows the potential value of home-based CCM for participants, organizations and policymakers. Future research is needed to examine potential cost savings.

Integrated collaborative care intervention for depression and obesity in primary care: translation from research to practice.

The objective of this study was to present lessons learned about engagement, delivery modality and pandemic impact while delivering a collaborative care intervention with a socioeconomically, racially and ethnically diverse sample. Participants completed a post-intervention survey (n = 41) on experiences and preferred intervention delivery modality, coronavirus 2019 (COVID-19) Impact Survey (n = 50) and provided open-ended feedback about the intervention (n = 27). Intervention process data included attendance, modality, and withdrawals. Data were analyzed using descriptive statistics and inductive content analyses. Of 71 intervention participants, 6 (8%) withdrew before session 1. Completers adhered to intervention timeline better than withdrawals. Participants liked the in-person interaction, efficient coach support, accountability of in-person and Zoom vs. phone sessions and the flexibility and convenience of phone and Zoom vs. in-person sessions. A majority of participants reported experiencing pandemic impacts such as heightened emotional distress, decreased activity engagement, poorer eating behaviors and being unable to meet basic needs. Participants deviating from intervention timelines may be re-engaged by targeted outreach attempts. Videoconference has the potential for providing as-needed coaching. Future interventions may be optimized to account for and address areas impacted by the pandemic. Findings revealed specific strategies that can be implemented in future interventions to improve emotional and physical health among diverse populations.

Cross-trial prediction of depression remission using problem-solving therapy: A machine learning approach.

BACKGROUND: Psychotherapy is a standard depression treatment; however, determining a patient's prognosis with therapy relies on clinical judgment that is subject to trial-and-error and provider variability. PURPOSE: To develop machine learning (ML) algorithms to predict depression remission for patients undergoing 6 months of problem-solving therapy (PST). METHOD: Using data from the treatment arm of 2 randomized trials, ML models were trained and validated on ENGAGE-2 (ClinicalTrials.gov, #NCT03841682) and tested on RAINBOW (ClinicalTrials.gov, #NCT02246413) for predictions at baseline and at 2-months. Primary outcome was depression remission using the Depression Symptom Checklist (SCL-20) score < 0.5 at 6 months. Predictor variables included baseline characteristics (sociodemographic, behavioral, clinical, psychosocial) and intervention engagement through 2-months. RESULTS: Of the 26 candidate variables, 8 for baseline and 11 for 2-months were predictive of depression remission, and used to train the models. The best-performing model predicted remission with an accuracy significantly greater than chance in internal validation using the ENGAGE-2 cohort, at baseline [72.6% (SD = 3.6%), p < 0.0001] and at 2-months [72.3% (5.1%), p < 0.0001], and in external validation with the RAINBOW cohort at baseline [58.3% (0%), p < 0.0001] and at 2-months [62.3% (0%), p < 0.0001]. Model-agnostic explanations highlighted key predictors of depression remission at the cohort and patient levels, including female sex, lower self-reported sleep disturbance, lower sleep-related impairment, and lower negative problem orientation. CONCLUSIONS: ML models using clinical and patient-reported data can predict depression remission for patients undergoing PST, affording opportunities for prospective identification of likely responders, and for developing personalized early treatment optimization along the patient care trajectory.

Partnering with community-based organizations to improve equitable access to depression care for underserved older adults in the U.S.: Qualitative formative research.

Background: Embedding evidenced-based programs (EBPs) like PEARLS outside clinical settings can help reduce inequities in access to depression care. Trusted community-based organizations (CBOs) reach older adults who are underserved; however, PEARLS adoption has been limited. Implementation science has tried to close this know-do gap, however a more intentional focus on equity is needed to engage CBOs. We partnered with CBOs to better understand their resources and needs in order to design more equitable dissemination and implementation (D&I) strategies to support PEARLS adoption. Methods: We conducted 39 interviews with 24 current and potential adopter organizations and other partners (February-September 2020). CBOs were purposively sampled for region, type, and priority older populations experiencing poverty (communities of color, linguistically diverse, rural). Using a social marketing framework, our guide explored barriers, benefits and process for PEARLS adoption; CBO capacities and needs; PEARLS acceptability and adaptations; and preferred communication channels. During COVID-19, interviews also addressed remote PEARLS delivery and changes in priorities. We conducted thematic analysis of transcripts using the rapid framework method to describe the needs and priorities of older adults who are underserved and the CBOs that engage them, and strategies, collaborations, and adaptations to integrate depression care in these contexts. Results: During COVID-19, older adults relied on CBO support for basic needs such as food and housing. Isolation and depression were also urgent issues within communities, yet stigma remained for both late-life depression and depression care. CBOs wanted EBPs with cultural flexibility, stable funding, accessible training, staff investment, and fit with staff and community needs and priorities. Findings guided new dissemination strategies to better communicate how PEARLS is appropriate for organizations that engage older adults who are underserved, and what program components are core and what are adaptable to better align with organizations and communities. New implementation strategies will support organizational capacity-building through training and technical assistance, and matchmaking for funding and clinical support. Discussion: Findings support CBOs as appropriate depression care providers for older adults who are underserved, and suggest changes to communications and resources to better fit EBPs with the resources and needs of organizations and older adults. We are currently partnering with organizations in California and Washington to evaluate whether and how these D&I strategies increase equitable access to PEARLS for older adults who are underserved.

Problem-solving therapy-induced amygdala engagement mediates lifestyle behavior change in obesity with comorbid depression: a randomized proof-of-mechanism trial.

BACKGROUND: Depression hinders obesity treatment; elucidating mechanisms may enable treatment enhancements. OBJECTIVES: The aim was to investigate whether changes in neural targets in the negative affect circuit following psychotherapy mediate subsequent changes in weight and behaviors. METHODS: Adults (n = 108) with obesity and depression were randomly assigned to usual care or an intervention that delivered problem-solving therapy (PST) for depression over 2 mo. fMRI for brain imaging was performed at baseline and 2 mo. BMI, physical activity, and diet were measured at baseline and 12 mo. Mediation analysis assessed between-group differences in neural target changes using t test and correlations between neural target changes and outcome changes (simple and interaction effect) using ordinary least-squares regression. RESULTS: Compared with usual care, PST led to reductions in left amygdala activation (-0.75; 95% CI: -1.49, -0.01) and global scores of the negative affect circuit (-0.43; -0.81, -0.06), engaged by threat stimuli. Increases in amygdala activation and global circuit scores at 2 mo correlated with decreases in physical activity outcomes at 12 mo in the usual-care group; these relations were altered by PST. In relation to change in leisure-time physical activity, standardized ß-coefficients were -0.67 in usual care and -0.01 in the intervention (between-group difference: 0.66; 0.02, 1.30) for change in left amygdala activation and -2.02 in usual care and -0.11 in the intervention (difference: 1.92; 0.64, 3.20) for change in global circuit scores. In relation to change in total energy expenditure, standardized ß-coefficients were -0.65 in usual care and 0.08 in the intervention (difference: 0.73; 0.29, 1.16) for change in left amygdala activation and -1.65 in usual care and 0.08 in the intervention (difference: 1.74; 0.85, 2.63) for change in global circuit scores. Results were null for BMI and diet. CONCLUSIONS: Short-term changes in the negative affect circuit engaged by threat stimuli following PST for depression mediated longer-term changes in physical activity. This trial was registered at www.clinicaltrials.gov as NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).

Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial.

BACKGROUND: Depression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity. METHODS: This study ('ENGAGE') was a pre-planned element of the randomized controlled trial, 'RAINBOW' (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy ('PST')). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach. FINDINGS: PST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability. INTERPRETATION: The negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity. FUNDING: US National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368.

Using RE-AIM to examine the potential public health impact of an integrated collaborative care intervention for weight and depression management in primary care: Results from the RAINBOW trial.

BACKGROUND: An integrated collaborative care intervention was used to treat primary care patients with comorbid obesity and depression in a randomized clinical trial. To increase wider uptake and dissemination, information is needed on translational potential. METHODS: The trial collected longitudinal, qualitative data at baseline, 6 months (end of intensive treatment), 12 months (end of maintenance treatment), and 24 months (end of follow-up). Semi-structured interviews (n = 142) were conducted with 54 out of 409 randomly selected trial participants and 37 other stakeholders, such as recruitment staff, intervention staff, and clinicians. Using a Framework Analysis approach, we examined themes across time and stakeholder groups according to the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. RESULTS: At baseline, participants and other stakeholders reported being skeptical of the collaborative care approach related to some RE-AIM dimensions. However, over time they indicated greater confidence regarding the potential for future public health impact. They also provided information on barriers and actionable information to enhance program reach, effectiveness, adoption, implementation, and maintenance. CONCLUSIONS: RE-AIM provided a useful framework for understanding how to increase the impact of a collaborative and integrative approach for treating comorbid obesity and depression. It also demonstrates the utility of using the framework as a planning tool early in the evidence-generation pipeline.

Sex Moderates Treatment Effects of Integrated Collaborative Care for Comorbid Obesity and Depression: The RAINBOW RCT.

BACKGROUND: Sex influences health and related behaviors due to biological and psychosocial/socioeconomic factors. Assessing sex-specific responses to integrated treatment for comorbid obesity and depression could inform intervention targeting. PURPOSE: To test (a) whether sex moderates the effects of integrated collaborative care on weight and depression outcomes through 24 months and (b) whether treatment response at 6 months predicts 12 and 24 month outcomes by sex. METHODS: Secondary data analyses on weight and depression severity (SCL-20) measured over 24 months among 409 adults with obesity and depression in the Research Aimed at Improving Both Mood and Weight trial. RESULTS: Men achieved significantly greater weight reductions in intervention versus usual care than women, whereas women achieved significantly greater percentage reductions in SCL-20 than men at both 12 and 24 months. In logistic models, at 80% specificity for correctly identifying participants not achieving clinically significant long-term outcomes, women who lost <3.0% weight and men who lost <4.1% weight at 6 months had ≥84% probability of not meeting 5% weight loss at 24 months. Similarly, at 80% specificity, women who reduced SCL-20 by <39.5% and men who reduced by <53.0% at 6 months had ≥82% probability of not meeting 50% decrease in SCL-20 at 24 months. CONCLUSIONS: Sex modified the integrated treatment effects for obesity and depression. Sex-specific responses at 6 months predicted clinically significant weight loss and depression outcomes through 24 months. Based on early responses, interventions may need to be tailored to address sex-specific barriers and facilitators to achieving healthy weight and depression outcomes at later time points. CLINICAL TRIAL REGISTRATION: NCT02246413 (https://clinicaltrials.gov/ct2/show/NCT02246413).

Understanding mechanisms of integrated behavioral therapy for co-occurring obesity and depression in primary care: a mediation analysis in the RAINBOW trial.

The RAINBOW trial demonstrated that an integrated collaborative care intervention was effective for improving weight and depression. This study examined mediation of the treatment effect by a priori specified lifestyle behaviors and cognitive functioning. Participants were randomized to a 12-month integrated intervention (n = 204) or usual care (n = 205). Body mass index (BMI) and 20-item Depression Symptom Check List (SCL-20) were co-primary outcomes (Y). To examine mediation, we assessed (a) the effect of the integrated intervention (X) on lifestyle behaviors (diet and physical activity) and cognitive functioning (problem-solving; M, X→M path a) and (b) the association of these behaviors with BMI and SCL-20 (M→Y path b). Mediation existed if paths a and b were significant or if path a and the product of coefficients test (paths a and b) were significant. Compared with usual care, the intervention led to significant improvements in leisure time physical activity (201.3 MET minutes/week [SD, 1,457.6]) and total calorie intake (337.4 kcal/day [818.3]) at 6 months but not 12 months (path a). These improvements were not significantly associated with improvements in BMI or SCL-20 (path b). However, avoidant problem-solving style score and increased fruit and vegetable intake significantly correlated with improvements in BMI at 6 and 12 months, respectively. Also, increased fruit and vegetable intake, higher dietary quality, and better problem-solving abilities significantly correlated with improvements in SCL-20 at 6 and 12 months. These findings did not support the hypothesized mediation, but suggest lifestyle behaviors and cognitive functioning to target in future intervention optimization.

Increasing Social Connectedness for Underserved Older Adults Living With Depression: A Pre-Post Evaluation of PEARLS.

OBJECTIVE: To evaluate PEARLS effectiveness for increasing social connectedness among underserved older adults with depression. DESIGN: Multisite, pre-post single-group evaluation. SETTING: Community-based social service organizations (N = 16) in five U.S. states, purposively sampled for maximum variation of participants and providers. PARTICIPANTS: A total of 320 homebound older adults (mean(SD) age 72.9(9.6), 79% female, 44% people of color, 81% low-income, 61% living alone, average four chronic conditions) with clinically significant depression (PHQ-9 mean(SD) 12.7(4.6)). INTERVENTION: Four to 6 month home-based depression care management model delivered by trained front-line providers. MEASUREMENTS: Brief validated social connectedness scales: Duke Social Support Index 10-item (DSSI-10), PROMIS-Social Isolation (6-item), UCLA-Loneliness (3-item); sociodemographic and health measures. RESULTS: At baseline, PEARLS participants overall and with ≥1 of the following characteristics were less socially connected: younger (50-64), white, LGBTQ+, not partnered, not caregiving, living alone, financial limitations, chronic conditions, and/or recently hospitalized. Six-months post-PEARLS enrollment, participants significantly increased social interactions and satisfaction with social support (DSSI-10 t[312] = 5.2, p <0.001); and reduced perceived isolation (PROMIS t[310] = 6.3, p <0.001); and loneliness (UCLA t[301] = 3.7, p =0.002), with small to moderate effect sizes (Cohen's d DSSI-10: 0.28, PROMIS-SI: 0.35, UCLA: 0.21). Increased social connectedness was associated with reduced depression. Improvements in social connectedness (except social interactions) persisted during early COVID-19. Being Latino and/or having difficulty paying for basic needs was associated with less improvement in post-PEARLS social connectedness. CONCLUSION: PEARLS has potential to improve social connectedness among underserved older adults, though additional supports may be needed for persons facing multiple social determinants of health. Further research is needed to establish causality.

The factor structure of depressive symptoms in patients with obesity enrolled in the RAINBOW clinical trial.

BACKGROUND: Examining variability in the presenting symptoms of depression may be particularly important in characterizing depression in patients with comorbid conditions such as obesity. Identifying the underlying constructs of depression in such patients may produce phenotypic information to aid diagnosis and treatment decisions. OBJECTIVE: To examine the latent factors of symptoms using the depression Symptom Checklist (SCL-20) and the Patient Health Questionnaire (PHQ-9), separately, in patients with obesity and elevated depressive symptoms. METHODS: Exploratory factor analysis (EFA) was performed on baseline data from 409 patients with obesity and elevated depressive symptoms recruited in primary care. Bootstrap analysis was performed to estimate the precision and potential replicability of identified latent factors. RESULTS: Participants (70% women, mean age of 51.0 ± 12.1 years) had moderate depression. EFA of the SCL-20 suggested two reliable factors: dysphoric mood (71% of the variance) and anhedonia (15% of the variance). EFA of the PHQ-9 yielded one factor: dysphoric mood (87% of the variance). Bootstrapped results supported the replicability of these results. The top most endorsed symptoms were feeling low energy, overeating and disturbed sleep. LIMITATIONS: The generalizability of these findings to severe depression may be limited. CONCLUSIONS: Patients with elevated depressive symptoms and obesity present with heterogeneous symptoms. The SCL-20 seems more sensitive than the PHQ-9 for differentiating symptom profiles in this population. Some possible reasons include: 1) differences in number of scale items, and 2) differences in the aspects of depression they tap into; the SCL-20 measures the severity of symptoms, whereas the PHQ-9 measures the frequency of symptoms.

Correction: Variability in engagement and progress in efficacious integrated collaborative care for primary care patients with obesity and depression: Within-treatment analysis in the RAINBOW trial.

[This corrects the article DOI: 10.1371/journal.pone.0231743.].

The ENGAGE-2 study: Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes in a randomized controlled trial (Phase 2).

Despite evidence for effective integrated behavior therapy for treating comorbid obesity and depression, treatment response is highly variable and the underlying neurobiological mechanisms remain unknown. This hampers efforts to identify mechanistic targets in order to optimize treatment precision and potency. Funded within the NIH Science of Behavior Change (SOBC) Research Network, the 2-phased ENGAGE research project applies an experimental precision medicine approach to address this gap. The Phase 1 study focused on demonstrating technical feasibility, target engagement and potential neural mechanisms of responses to an integrated behavior therapy. This therapy combines a video-based behavioral weight loss program and problem-solving therapy for depression, with as-needed intensification of antidepressant medications, and its clinical effectiveness was demonstrated within a parent randomized clinical trial. Here, we describe the ENGAGE Phase 2 (ENGAGE-2) study protocol which builds on Phase 1 in 2 ways: (1) pilot testing of an motivational interviewing-enhanced, integrated behavior therapy in an independent, primarily minority patient sample, and (2) evaluation of a priori defined neural targets, specifically the negative affect (threat and sadness) circuits which demonstrated engagement and malleability in Phase 1, as mediators of therapeutic outcomes. Additionally, the Phase 2 study includes a conceptual and methodological extension to explore the role of microbiome-gut-brain and systemic immunological pathways in integrated behavioral treatment of obesity and depression. This protocol paper documents the conceptualization, design and the transdisciplinary methodologies in ENGAGE-2, which can inform future clinical and translational research in experimental precision medicine for behavior change and chronic disease management. Trial registration: ClinicalTrials.gov #NCT 03,841,682.

First-Year Economic and Quality of Life Effects of the RAINBOW Intervention to Treat Comorbid Obesity and Depression.

OBJECTIVE: Obesity and depression are prevalent and often co-occurring conditions in the United States. The Research Aimed at Improving Both Mood and Weight (RAINBOW) randomized trial demonstrated the effectiveness of an integrated intervention for adults with both conditions. Characterizing the intervention's economic effects is important for broader dissemination and implementation. METHODS: This study evaluated the cost (2018 US dollars) and health-related quality of life (HRQoL) impacts during RAINBOW's first year, comparing intervention (n = 204) and usual-care groups (n = 205). Outcomes included intervention delivery costs, differential changes in antidepressant medication spending compared with the pretrial year, differential changes in medical services spending compared with the pretrial year, and HRQoL changes from baseline using Euroqol-5D US utility weights. RESULTS: RAINBOW's 1-year delivery cost per person was $2,251. Compared with usual care, annual antidepressant medication days increased more (38 days [95% CI: 4 to 72]; P = 0.027). Annual antidepressant medication spending had a larger, nonsignificant increase ($89 [95% CI: -$20 to $197]; P = 0.109). Annual spending on medical care services had a smaller, nonsignificant decrease (-$54 [95% CI: -$832 to $941]; P = 0.905). HRQoL had a nonsignificant increase (0.011 [95% CI: -0.025 to 0.047]; P = 0.546). CONCLUSIONS: The RAINBOW intervention's economic value will depend on how its 1-year improvements in obesity and depression translate into long-term reduced morbidity, delayed mortality, or averted costs.

Variability in engagement and progress in efficacious integrated collaborative care for primary care patients with obesity and depression: Within-treatment analysis in the RAINBOW trial.

INTRODUCTION: The RAINBOW randomized clinical trial validated the efficacy of an integrated collaborative care intervention for obesity and depression in primary care, although the effect was modest. To inform intervention optimization, this study investigated within-treatment variability in participant engagement and progress. METHODS: Data were collected in 2014-2017 and analyzed post hoc in 2018. Cluster analysis evaluated patterns of change in weekly self-monitored weight from week 6 up to week 52 and depression scores on the Patient Health Questionnaire-9 (PHQ-9) from up to 15 individual sessions during the 12-month intervention. Chi-square tests and ANOVA compared weight loss and depression outcomes objectively measured by blinded assessors to validate differences among categories of treatment engagement and progress defined based on cluster analysis results. RESULTS: Among 204 intervention participants (50.9 [SD, 12.2] years, 71% female, 72% non-Hispanic White, BMI 36.7 [6.9], PHQ-9 14.1 [3.2]), 31% (n = 63) had poor engagement, on average completing self-monitored weight in <3 of 46 weeks and <5 of 15 sessions. Among them, 50 (79%) discontinued the intervention by session 6 (week 8). Engaged participants (n = 141; 69%) self-monitored weight for 11-22 weeks, attended almost all 15 sessions, but showed variable treatment progress based on patterns of change in self-monitored weight and PHQ-9 scores over 12 months. Three patterns of weight change (%) represented minimal weight loss (n = 50, linear ß1 = -0.06, quadratic ß2 = 0.001), moderate weight loss (n = 61, ß1 = -0.28, ß2 = 0.002), and substantial weight loss (n = 12, ß1 = -0.53, ß2 = 0.005). Three patterns of change in PHQ-9 scores represented moderate depression without treatment progress (n = 40, intercept ß0 = 11.05, ß1 = -0.11, ß2 = 0.002), moderate depression with treatment progress (n = 20, ß0 = 12.90, ß1 = -0.42, ß2 = 0.006), and milder depression with treatment progress (n = 81, ß0 = 7.41, ß1 = -0.23, ß2 = 0.003). The patterns diverged within 6-8 weeks and persisted throughout the intervention. Objectively measured weight loss and depression outcomes were significantly worse among participants with poor engagement or poor progress on either weight or PHQ-9 than those showing progress on both. CONCLUSIONS: Participants demonstrating poor engagement or poor progress could be identified early during the intervention and were more likely to fail treatment at the end of the intervention. This insight could inform individualized and timely optimization to enhance treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov# NCT02246413.

Effect of an Intervention for Obesity and Depression on Patient-Centered Outcomes: An RCT.

INTRODUCTION: An integrated collaborative care intervention was successful for treating comorbid obesity and depression. The effect of the integrated intervention on secondary outcomes of quality of life and psychosocial functioning were examined, as well as whether improvements in these secondary outcomes were correlated with improvements in the primary outcomes of weight and depressive symptoms. STUDY DESIGN: This RCT compared an integrated collaborative care intervention for obesity and depression to usual care. Data were analyzed in 2018. SETTING/PARTICIPANTS: Adult primary care patients (n=409) with a BMI ≥30 (≥27 if Asian) and 9-Item Patient Health Questionnaire score ≥10 were recruited from September 30, 2014 to January 12, 2017 from primary care clinics in Northern California. INTERVENTION: The 12-month intervention integrated a behavioral weight loss program and problem-solving therapy with as-needed antidepressant medications for depression. MAIN OUTCOME MEASURES: A priori secondary outcomes included health-related quality of life (Short Form-8 Health Survey), obesity-specific quality of life (Obesity-Related Problems Scale), sleep disturbance and sleep-related impairment (Patient-Reported Outcomes Measurement Information System), and functional disability (Sheehan Disability Scale) at baseline and 6 and 12 months. RESULTS: Participants randomized to the intervention experienced significantly greater improvements in obesity-specific problems, mental health-related quality of life, sleep disturbance, sleep-related impairment, and functional disability at 6 months but not 12 months. Improvements in obesity-related problems (ß=0.01, 95% CI=0.01, 0.02) and sleep disturbance (ß= -0.02, 95% CI= -0.04, 0) were associated with lower BMI. Improvements in the physical (ß= -0.01, 95% CI= -0.01, 0) and mental health components (ß= -0.02, 95% CI= -0.03, -0.02) of the Short Form-8 Health Survey as well as sleep disturbance (ß=0.01, 95% CI=0.01, 0.02) and sleep-related impairment (ß=0.01, 95% CI=0, 0.01) were associated with fewer depressive symptoms. CONCLUSIONS: An integrated collaborative care intervention for obesity and depression that was shown previously to improve weight and depressive symptoms may also confer benefits for quality of life and psychosocial functioning over 6 months. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov NCT02246413.

Effect of Integrated Behavioral Weight Loss Treatment and Problem-Solving Therapy on Body Mass Index and Depressive Symptoms Among Patients With Obesity and Depression: The RAINBOW Randomized Clinical Trial.

Importance: Coexisting obesity and depression exacerbate morbidity and disability, but effective treatments remain elusive. Objective: To test the hypothesis that an integrated collaborative care intervention would significantly improve both obesity and depression at 12 months compared with usual care. Design, Setting, and Participants: The Research Aimed at Improving Both Mood and Weight (RAINBOW) randomized clinical trial enrolled 409 adults with body mass indices (BMIs) of 30 or greater (≥27 for Asian adults) and 9-item Patient Health Questionnaire (PHQ-9) scores of 10 or greater. Primary care patients at a health system in Northern California were recruited from September 30, 2014, to January 12, 2017; the date of final 12-month follow-up was January 17, 2018. Interventions: All participants randomly assigned to the intervention (n = 204) or the usual care control group (n = 205) received medical care from their personal physicians as usual, received information on routine services for obesity and depression at their clinic, and received wireless physical activity trackers. Intervention participants also received a 12-month intervention that integrated a Diabetes Prevention Program-based behavioral weight loss treatment with problem-solving therapy for depression and, if indicated, antidepressant medications. Main Outcomes and Measures: The co-primary outcome measures were BMI and 20-item Depression Symptom Checklist (SCL-20) scores (range, 0 [best] to 4 [worst]) at 12 months. Results: Among 409 participants randomized (mean age of 51.0 years [SD, 12.1 years]; 70% were women; mean BMI of 36.7 [SD, 6.4]; mean PHQ-9 score of 13.8 [SD, 3.1]; and mean SCL-20 score of 1.5 [SD, 0.5]), 344 (84.1%) completed 12-month follow-up. At 12 months, mean BMI declined from 36.7 (SD, 6.9) to 35.9 (SD, 7.1) among intervention participants compared with a change in mean BMI from 36.6 (SD, 5.8) to 36.6 (SD, 6.0) among usual care participants (between-group mean difference, -0.7 [95% CI, -1.1 to -0.2]; P = .01). Mean SCL-20 score declined from 1.5 (SD, 0.5) to 1.1 (SD, 1.0) at 12 months among intervention participants compared with a change in mean SCL-20 score from 1.5 (SD, 0.6) to 1.4 (SD, 1.3) among usual care participants (between-group mean difference, -0.2 [95% CI, -0.4 to 0]; P = .01). There were 47 adverse events or serious adverse events that involved musculoskeletal injuries (27 in the intervention group and 20 in the usual care group). Conclusions and Relevance: Among adults with obesity and depression, a collaborative care intervention integrating behavioral weight loss treatment, problem-solving therapy, and as-needed antidepressant medications significantly improved weight loss and depressive symptoms at 12 months compared with usual care; however, the effect sizes were modest and of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02246413.