Trajectories of remitted psychotic depression: identification of predictors of worsening by machine learning.

BACKGROUND: Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory. METHOD: One hundred and twenty-six persons aged 18-85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics. RESULTS: Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model. CONCLUSIONS: Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Advanced Research Institute (ARI): Supporting the Geriatric Mental Health Research Pipeline.

The Advanced Research Institute (ARI) in Mental Health and Aging is a NIMH-funded mentoring network to help transition early-career faculty to independent investigators and scientific leaders. Since 2004, ARI has enrolled 184 Scholars from 61 institutions across 34 states. We describe the ARI components and assess the impact and outcomes of ARI on research careers of participants. Outcomes of ARI graduates (n = 165) came from NIH Reporter, brief surveys, and CVs: 87.3% remained active researchers, 83.6% performed scientific service, and 80.6% obtained federal grants. A population-based analysis examined NIMH mentored K awardees initially funded from 2002-2018 (n = 1160): in this group, 77.1% (47/61) of ARI participants versus 49.5% (544/1099) of nonparticipants obtained an R01. Controlling for time, ARI participants were 3.2 times more likely to achieve R01 funding than nonparticipants. Given the struggle to reduce attrition from the research career pipeline, the effectiveness of ARI model could be relevant to other fields.

Research-Practice Partnership to Develop and Implement Routine Mental Health Symptom Tracking Tool Among Older Adults During COVID-19.

OBJECTIVE: Older adults are disproportionally impacted by the COVID-19 pandemic, causing a mental health crisis in late life, due to physical restrictions (e.g., quarantine), limited access to services, and lower literacy and access to technology. Despite established benefits, systematic screening of mental health needs of older adults in community and routine care settings is limited and presents multiple challenges. Cross-disciplinary collaborations are essential for identification and evaluation of mental health needs and service delivery. METHODS: Using a research-practice partnership model, we developed and implemented a routine mental health needs identification and tracking tool at a community-based social services organization. Repeated screenings were conducted remotely over 5 months and included depression, anxiety, perceived loneliness, social support, and related domains such as sleep quality, resilience, and trauma symptoms linked to COVID-19. We examined symptomatic distress levels and associations between different domains of functioning. RESULTS: Our project describes the process of establishing a research-practice partnership during the COVID-19 pandemic. We collected 292 screenings from 124 individuals; clients were mildly to moderately depressed and anxious, reporting large amounts of time alone and moderate levels of loneliness. Those reporting higher depressive symptoms reported higher anxiety symptoms, poorer sleep quality, lower quality of life, lower capacity to adapt to challenging situations, and greater trauma symptoms due to COVID-19. CONCLUSION: Our routine screening tool can serve as a blueprint for case management agencies and senior centers nationwide, beyond the pressing mental health crisis due to COVID-19, to continue identifying needs as they emerge in the community.

Improved outcomes for depressed elder abuse victims with video-delivered psychotherapy during COVID-19.

OBJECTIVE: There is a lack of evidence-based scalable therapies for elder abuse victims, with no current remotely delivered tailored psychotherapy. The purpose of this manuscript is to (a) examine the effectiveness of a brief therapy for depression for elder abuse victims, and (b) to compare remote intervention delivery via phone or video to the traditional in-person delivery. METHOD: PROTECT, Providing Options to Elderly Clients Together, is a brief therapy developed in collaboration with partners at the Department for the Aging (DFTA) of New York City. During the COVID-19 outbreak, PROTECT delivery shifted from in-person to phone or video delivery. Depression severity was tracked using the Patient Health Questionaire-9 (PHQ-9). Reduction in depression severity was evaluated using a linear mixed effects model with non-inferiority test to compare the effectiveness of video vs in-person delivery of PROTECT. RESULTS: PROTECT reduced depression (average 5.15 PHQ-9 points). Video and phone delivery were non-inferior to in-person delivery. The video group completed therapy more quickly than the in-person group and had a more rapid improvement in depression symptoms. CONCLUSIONS: PROTECT therapy delivered remotely reduces depression among diverse elder abuse victims. Video delivery of PROTECT could increase reach and scalability to serve more vulnerable older depressed victims.

Modifiable predictors of nonresponse to psychotherapies for late-life depression with executive dysfunction: a machine learning approach.

The study aimed to: (1) Identify distinct trajectories of change in depressive symptoms by mid-treatment during psychotherapy for late-life depression with executive dysfunction; (2) examine if nonresponse by mid-treatment predicted poor response at treatment end; and (3) identify baseline characteristics predicting an early nonresponse trajectory by mid-treatment. A sample of 221 adults 60 years and older with major depression and executive dysfunction were randomized to 12 weeks of either problem-solving therapy or supportive therapy. We used Latent Growth Mixture Models (LGMM) to detect subgroups with distinct trajectories of change in depression by mid-treatment (6th week). We conducted regression analyses with LGMM subgroups as predictors of response at treatment end. We used random forest machine learning algorithms to identify baseline predictors of LGMM trajectories. We found that ~77.5% of participants had a declining trajectory of depression in weeks 0-6, while the remaining 22.5% had a persisting depression trajectory, with no treatment differences. The LGMM trajectories predicted remission and response at treatment end. A random forests model with high prediction accuracy (80%) showed that the strongest modifiable predictors of the persisting depression trajectory were low perceived social support, followed by high neuroticism, low treatment expectancy, and low perception of the therapist as accepting. Our results suggest that modifiable risk factors of early nonresponse to psychotherapy can be identified at the outset of treatment and addressed with targeted personalized interventions. Therapists may focus on increasing meaningful social interactions, addressing concerns related to treatment benefits, and creating a positive working relationship.

Comparing the streamlined psychotherapy "Engage" with problem-solving therapy in late-life major depression. A randomized clinical trial.

Effective psychotherapies for late-life depression are underutilized, mainly because of their complexity. "Engage" is a novel, streamlined psychotherapy that relies on neurobiology to identify core behavioral pathology of late-life depression and targets it with simple interventions, co-designed with community therapists so that they can be delivered in community settings. Consecutively recruited adults (≥60 years) with major depression (n = 249) were randomly assigned to 9 weekly sessions of "Engage" or to the evidence-based Problem-Solving Therapy (PST) offered by 35 trained community social workers and assessed by blind raters. "Engage" therapists required an average of 30% less training time to achieve fidelity to treatment than PST therapists and had one-third of the PST therapists' skill drift. Both treatments led to reduction of HAM-D scores over 9 weeks. The mixed effects model-estimated HAM-D ratings were not significantly different between the two treatments at any assessment point of the trial. The one-sided 95% CI for treatment-end difference was (-∞, 0.07) HAM-D points, indicating a non-inferiority margin of 1.3 HAM-D points or greater; this margin is lower than the pre-determined 2.2-point margin. The two treatment arms had similar response (HR = 1.08, 95% CI (0.76, 1.52), p = 0.67) and remission rates (HR = 0.89, 95% CI (0.57, 1.39), p = 0.61). We conclude that "Engage" is non-inferior to PST. If disseminated, "Engage" will increase the number of therapists who can reliably treat late-life depression and make effective psychotherapy available to large numbers of depressed older adults.

Perceived Social Support and Interpersonal Functioning as Predictors of Treatment Response Among Depressed Older Adults.

OBJECTIVE: Social isolation is highly common in late life and is associated with devastating mental health and physical outcomes. This study investigated whether components of social isolation (marital status, perceived social support, and interpersonal problems) predict change in depression severity over the course of a brief adherence intervention delivered in a primary care setting. METHOD: A sample of 189 older adults with major depressive disorder were randomized to either an adherence intervention, "Treatment Initiation Program," or treatment as usual. Marital status, perceived social support and interpersonal problems were assessed at baseline. A mixed-effects regression was used to test whether these factors predicted the change trajectory in depression severity over 24 weeks. RESULTS: Being married (F(2,176) = 6.60; p = 0.001), reporting higher perceived social support (F(2,177) = 4.70; p = 0.01), and fewer interpersonal problems (F(2, 176) = 4.34; p = 0.01) predicted lower depression severity on average over the course of 24 weeks. CONCLUSION: Social variables such as living in partnership, perceiving others as supportive, and reporting few interpersonal problems may reduce older adults' vulnerability to depression and enhance their ability to benefit from treatment. These findings can guide development of interventions that will target these social factors early in treatment to increase efficacy.

PROTECT: a novel psychotherapy for late-life depression in elder abuse victims.

Elder abuse is prevalent, and victims have high rates of depression and low quality of life. We established an academic-community partnership to test the feasibility, acceptability, and impact of a brief psychotherapy for depression (PROTECT) among elder abuse victims with capacity to make decisions. Elder abuse service providers referred depressed (Patient Health Questionnaire-9 [PHQ-9] ≥ 10) older victims (age ≥ 55 years) for potential pilot study participation. Forty eligible victims who consented were randomized to PROTECT psychotherapy (N = 25) or a Usual Care (N = 15) condition involving a community psychotherapy referral. Follow-up research assessments were conducted at 6 weeks (mid-treatment) and 9 weeks (end of treatment) after study initial assessment. We used mixed-effects regression models to examine treatment effects on depression severity and quality of life over time. Most victims (75%) reported two or more types of abuse. The a priori acceptability benchmark was met at the end of PROTECT therapy. All PROTECT participants initiated therapy; this engagement rate is greater than the a priori 75% standard set for feasibility. We found a significant reduction in depression severity (Montgomery-Åsberg Depression Rating Scale [MADRS]), with PROTECT leading to greater benefits compared to Usual Care. Both study groups had a similar improvement in quality of life. The pilot project results found that PROTECT psychotherapy is feasible, acceptable, and effective in reducing depression. With the support of our partnership, we found that PROTECT could be delivered alongside elder abuse services with victims willing to initiate therapy that leads to meaningful treatment effects.

Associations between unmet palliative care needs and cognitive impairment in a sample of diverse, community-based older adults.

OBJECTIVE: Given a large number of community-based older adults with mild cognitive impairment, it is essential to better understand the relationship between unmet palliative care (PC) needs and mild cognitive impairment in community-based samples. METHOD: Participants consisted of adults ages 60+ receiving services at senior centers located in New York City. The Montreal Cognitive Assessment (MoCA) and the Unmet Palliative Care Needs screening tool were used to assess participants' cognitive status and PC needs. RESULTS: Our results revealed a quadratic relationship between unmet PC needs and mild cognitive impairment, controlling for gender, living status, and age. Participants with either low or high MoCA scores reported lower PC needs than participants with average MoCA scores, mean difference of the contrast (low and high vs. middle) = 2.15, P = 0.08. SIGNIFICANCE OF RESULTS: This study is a first step toward elucidating the relationship between cognitive impairment and PC needs in a diverse community sample of older adults. More research is needed to better understand the unique PC needs of older adults with cognitive impairment living in the community.

The Relationship Between Maladaptive Personality and Social Role Impairment in Depressed Older Adults in Primary Care.

Objective: Personality pathology is associated with impaired social functioning in adults, though further evidence is needed to examine the individual contributions of personality traits and processes to social functioning in depressed older adults. This study is a secondary analysis examining the relationship between maladaptive personality traits and processes and social role impairment in depressed older adults in primary care. Methods: Participants (N = 56) were 77% female and ranged in age between 55-89 (M = 66.82, SD = 8.75). Personality pathology was measured by maladaptive traits (NEO-FFI) and processes (Inventory of Interpersonal Problems; IIP-PD-15). Individual variable as well as combined predictive models of social role impairment were examined. Results: Higher neuroticism (ß = 0.30, p < .05), lower agreeableness (ß = -0.35 p < .001) and higher IIP-PD-15 (ß = 0.28, p < .01) scores predicted greater impairment in social role functioning. A combined predictive model of neuroticism and IIP-PD-15 scores predicted unique variance in social role impairment (R2 = .71). Conclusion: These results link select personality traits and interpersonal processes to social role impairment, suggesting that these are indicators of personality pathology in older adults. Clinical Implications: These findings lend preliminary support for clinical screening of personality pathology in depressed older adults utilizing both personality trait and process measures.

Treatment Adequacy and Adherence as Predictors of Depression Response in Primary Care.

OBJECTIVE: Primary care is the de facto mental health system in the United States where physicians treat large numbers of depressed older adults with antidepressant medication. This study aimed to examine whether antidepressant dosage adequacy and patient adherence are associated with depression response among middle-aged and older adults prescribed with antidepressants by their primary care provider. DESIGN: A secondary analysis was conducted on a sample drawn from a randomized controlled trial comparing Treatment as Usual to Treatment Initiation Program, an adherence intervention. Treatment Initiation Program improved adherence but not depression compared to Treatment as Usual (Sirey et al., 2017). For this analysis, we examined dosing adequacy and adherence at 6 and 12 weeks as predictors of depression response in both groups at 12 and 24 weeks. SETTING: Primary care practices. PARTICIPANTS: One hundred eighty-seven older adults with depression prescribed an antidepressant for depression by their primary care provider. MEASUREMENTS: Depression response was defined as 50% reduction on the Hamilton Rating Scale for Depression. Adherence was defined as taking 80% of doses at follow-up interviews (6 and 12 weeks). Patient-reported dosage and duration of antidepressant therapy was collected using the Composite Antidepressant Score (adequacy score of >3) at follow-up. RESULTS: Greater adherence, but not receipt of adequate dosage, was associated with higher likelihood of treatment response at both 12 (Odds ratio (OR) = 2.63; 95% Confidence Interval (CI), 1.19-5.84) and 24 weeks (OR = 3.09; 95% CI, 1.46-6.55). CONCLUSION: As physicians prescribe antidepressants to the diverse group of adults seen in primary care, special attention to patients' views and approach to adherence may improve depression outcomes.

Two Interventions for PatientsWith Major Depression and Severe Chronic Obstructive Pulmonary Disease: Impact on Quality of Life.

OBJECTIVE: Clinically significant depression occurs in approximately 40% of chronic obstructive pulmonary disease (COPD) patients, and both illnesses severely impair quality of life. This study tests the hypothesis that problem-solving integrated with a treatment adherence intervention, the Problem Solving-Adherence (PSA), is superior to a personalized treatment adherence intervention, the Personalized Intervention for Depressed Patients with COPD (PID-C), alone in improving quality of life in depressed COPD patients. METHODS: After screening 633 admissions for acute rehabilitation, we studied quality of life in 87 participants with major depression (by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and severe COPD randomly assigned to 14 sessions of PID-C or PSA over 26 weeks. Quality of life was assessed using the Word Health Organization Quality of Life-BREF at baseline and weeks 10, 14, and 26. RESULTS: The hypothesis was not supported. Exploratory latent class growth modeling identified two quality of life trajectories. In 80.5% of participants, quality of life remained unchanged and improved in the remaining 19.5% during the first 14 weeks. Patients with a stable quality trajectory had higher qualityof life at baseline and a stronger sense of personal agency. CONCLUSION: Maintaining quality of life is a favorable outcome in depressed patients with COPD whose course is one of deterioration. These findings highlight the usefulness of PID-C, an easy to learn, personalized adherence enhancement intervention that, after further testing, may be integrated into the rehabilitation and care of depressed COPD patients.

Engagement in Socially and Interpersonally Rewarding Activities as a Predictor of Outcome in "Engage" Behavioral Activation Therapy for Late-Life Depression.

OBJECTIVE: Loneliness and social isolation are associated with depressive symptoms, cognitive and physical disabilities, and increased risk of mortality among older adults. Socially rewarding activities reduce loneliness, and neurobiological evidence suggests that these activities may activate neural reward systems in older adults to a greater extent than other rewarding experiences. The current study was designed to investigate whether engagement in social and interpersonal activities (i.e., exposure to social rewards) predicts subsequent increase in behavioral activation and reduction in depressive symptoms in reward exposure treatment for late-life depression. METHODS: Forty-eight older adults without cognitive impairment and with major depression received nine sessions of "Engage" psychotherapy. Behavioral activation and depression severity were assessed by trained raters at baseline and weeks 6 and 9. Patients' weekly behavioral plans were categorized into three groups: 1) solitary activities; 2) social-group activities (attending a social gathering or a social setting such as church or a senior center); and 3) interpersonal-individual activities (engaging in an interpersonal interaction with a specific friend or family member). RESULTS: Mixed-effects models showed reduction in depression severity and increase in behavioral activation over time. In linear regression models, a higher percentage of interpersonal-individual activities (but not solitary or social-group activities) predicted subsequent increase in behavioral activation and improvement of depression. CONCLUSION: These findings highlight the importance of understanding the effects of engagement in specific types of rewarding activities in behavioral activation treatments for late-life depression. Exposure to socially rewarding interpersonal interactions could contribute to the efficacy of psychotherapy for late-life depression.

Advanced Research Institute (ARI): An Effective Model for Career Development and Transition to Independence.

The vitality of geriatric mental health research requires an ongoing infusion of new investigators into the career pipeline. This report examines outcomes of the NIMH-funded, Advanced Research Institute (ARI) in Geriatric Mental Health, a national mentoring program supporting the transition of early career researchers to independent investigators. Outcome data for 119 ARI Scholars were obtained from the NIH Reporter database, CVs, and PubMed: 95.0% continue in research, 80.7% had obtained federal grants, and 45.4% had achieved an NIH R01. Among all NIMH mentored K awardees initially funded 2002-2014 (n=901), 60.4% (32/53) of ARI participants vs. 42.0% (356/848) of nonparticipants obtained an R01. Controlling for funding year, ARI participants were 1.9 times more likely to achieve R01 funding than nonparticipants. These data suggest that ARI has helped new generations of researchers to achieve independent funding, become scientific leaders, and conduct high impact research contributing to public health and patient care.

Lay-delivered behavioral activation for depressed senior center clients: Pilot RCT.

OBJECTIVE: We describe the development of a lay-delivered behavioral intervention ("Do More, Feel Better") for depressed senior center clients, and we present preliminary data from a pilot randomized controlled trial (RCT) on (a) the feasibility of training lay volunteers to fidelity and (b) the acceptability, impact, and safety of the intervention. METHODS: We trained 11 volunteers at two aging service settings in "Do More, Feel Better" and randomized 18 depressed clients to receive the intervention or referral to mental health services. RESULTS: Pilot data indicated that we can successfully train and certify 64% of older volunteers and that depressed clients receiving the intervention reported high levels of session attendance and satisfaction. While there were no significant differences in 12-week reduction in Hamilton Depression Rating Scale scores between groups, intervention clients showed an 8-point reduction in comparison with a 0-point reduction among referral clients. CONCLUSIONS: "Do More, Feel Better" has the potential of transferring evidence-based behavioral interventions to the hands of supervised lay volunteers and can address the insufficient workforce providing geriatric mental health services.

Two Interventions for Patients with Major Depression and Severe Chronic Obstructive Pulmonary Disease: Impact on Dyspnea-Related Disability.

OBJECTIVE: The Personalized Intervention for Depressed Patients with Chronic Obstructive Pulmonary Disease (PID-C) is an intervention aiming to help patients adhere to their rehabilitation and care. This study tested the hypothesis that the Problem-Solving Adherence (PSA) intervention, which integrates problem-solving into adherence enhancement procedures, reduces dyspnea-related disability more than PID-C. Exploratory analyses sought to identify patients with distinct dyspnea-related disability trajectories and to compare their clinical profiles. METHODS: In this randomized controlled trial in an acute inpatient rehabilitation and community, 101 participants diagnosed with chronic obstructive pulmonary disease (COPD) and major depression were included after screening 633 consecutive admissions for acute inpatient rehabilitation. Participants underwent 14 sessions of PID-C versus PSA over 26 weeks using the Pulmonary Functional Status and Dyspnea Questionnaire. RESULTS: The study hypothesis was not supported. Exploratory latent class growth modeling identified two distinct disability trajectories. Dyspnea-related disability improved in 39% of patients and remained unchanged in the rest. Patients whose dyspnea-related disability improved had more severe disability and less sense of control over their condition at baseline. CONCLUSION: Improvement or no worsening of disability was noted in both treatment groups. This is a favorable course for depressed patients with a severe, deteriorating medical illness. PID-C is compatible with the expertise of clinicians working in community-based rehabilitation programs, and after further testing in the community, it can be integrated in the care of depressed COPD patients.

Integrated Care for Depression in Older Primary Care Patients.

For decades, depression in older adults was overlooked and not treated. Most treatment was by primary care providers and typically poorly managed. Recent interventions that integrate mental health services into primary care have increased the number of patients who are treated for depression and the quality of that treatment. The most effective models involve systematic depression screening and monitoring, multidisciplinary teams that include primary care providers and mental health specialists, a depression care manager to work directly with patients over time and the use of guideline-based depression treatment. The article reviews the challenges and opportunities for providing high-quality depression treatment in primary care; describes the 3 major integrated care interventions, PRISM-E, IMPACT, and PROSPECT; reviews the evidence of their effectiveness, and adaptations of the model for other conditions and settings; and explores strategies to increase their scalability into real world practice.

Advances in Psychotherapy for Depressed Older Adults.

PURPOSE OF REVIEW: We review recent advances in psychotherapies for depressed older adults, in particular those developed for special populations characterized by chronic medical illness, acute medical illness, cognitive impairment, and suicide risk factors. We review adaptations for psychotherapy to overcome barriers to its accessibility in non-specialty settings such as primary care, homebound or hard-to-reach older adults, and social service settings. RECENT FINDINGS: Recent evidence supports the effectiveness of psychotherapies that target late-life depression in the context of specific comorbid conditions including COPD, heart failure, Parkinson's disease, stroke and other acute conditions, cognitive impairment, and suicide risk. Growing evidence supports the feasibility, acceptability, and effectiveness of psychotherapy modified for a variety of health care and social service settings. Research supports the benefits of selecting the type of psychotherapy based on a comprehensive assessment of the older adult's psychiatric, medical, functional, and cognitive status, and tailoring psychotherapy to the settings in which older depressed adults are most likely to present.