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.

Change in patient-centered outcomes of psychological well-being, sleep, and suicidality following treatment with intravenous ketamine for late-life treatment-resistant depression.

OBJECTIVE: To examine whether psychological well-being, sleep, and suicidality improved with treatment with intravenous (IV) ketamine for late-life treatment-resistant depression (TRD). METHODS: This is an analysis of secondary outcomes in an open-label late-life TRD study examining the safety, tolerability, and feasibility of IV ketamine infusions. In the acute phase, participants (N = 25) aged 60 years or older received twice-a-week IV ketamine for 4 weeks. Then, participants with Montgomery-Asberg Depression Rating Scale (MADRS) total score <10 or ≥ 30% reduction from baseline proceeded to the continuation phase, an additional four weeks of once-a-week IV ketamine. The secondary outcomes analyzed here are based on the National Institute of Health Toolbox Psychological Well-Being subscales for Positive Affect and General Life Satisfaction, the Pittsburgh Sleep Quality Index, and the Scale for Suicidal Ideation. RESULTS: Psychological well-being, sleep, and suicidality improved during the acute phase and those improvements were sustained during the continuation phase. Greater improvements in measures of psychological well-being and sleep were seen in participants who had greater improvements in MADRS scores and moved onto the continuation phase. All but one of the few participants with high suicidality at baseline improved; there were no cases of treatment-emergent suicidality. CONCLUSIONS: Psychological well-being, sleep, and suicidality improved in participants with late-life TRD who received IV ketamine for 8 weeks. A future larger and longer controlled trial is needed to confirm and extend these findings. REGISTRATION: ClinicalTrials.gov identifier: NCT04504175.

Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment.

Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption). Proper assessment and management is critical, as individuals with TRLLD often present in medical settings and suffer from cognitive decline and other marks of accelerated aging. This article serves as an evidence-based guide for medical practitioners who encounter TRLLD in their practice.

Interpersonal Support Domains Associated With Symptoms of Posttraumatic Stress Among Older Black and White Adults.

Objective: Older adults experience numerous changes in their social networks and social environment that may worsen preexisting posttraumatic stress disorder (PTSD) symptoms. This study tested whether tangible support, appraisal support, belonging support, and self-esteem were associated with trauma symptom burden among community-dwelling older Black and White adults at baseline and over 12 months of follow-up.Methods: This study used data collected from a randomized controlled trial for depression prevention in adults 50 years of age or older who had subsyndromal depression (2006-2011). Two hundred forty-four participants (including 90 older Black adults) were randomly assigned to a problem-solving therapy arm or an active control arm. The Interpersonal Support Evaluation List (ISEL) was administered at baseline and 12 months later. Linear regression analysis was used to examine associations of each of the ISEL dimensions with DSM-IV-defined PTSD symptoms at baseline and over time, with control for well-established correlates of PTSD including depression, anxiety, and sleep quality.Results: Participants were a mean (SD) of 65.6 (11.0) years of age, and 71% percent were female. Belongingness support was the only dimension of interpersonal support significantly associated with PTSD symptoms at baseline (ß = -0.192, t = -3.582, P < .001) and 12 months later (ß = -0.183, t = -2.735, P < .01). Regression models accounted for a large proportion of variance in PTSD symptoms. The association between belongingness support and PTSD symptoms did not vary by participant race.Conclusions: A strong perception of belongingness to family and/or friends was associated with fewer PTSD symptoms at baseline and over 12 months. This observation generates the hypothesis that behavioral interventions which directly target and modify interpersonal support may benefit both older Black and older White adults who have experienced trauma.Trial Registration: ClinicalTrials.gov identifier: NCT00326677.

Intravenous Ketamine for Late-Life Treatment-Resistant Depression: A Pilot Study of Tolerability, Safety, Clinical Benefits, and Effect on Cognition.

OBJECTIVE: Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. METHODS: In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week for 4 weeks; partial responders at the end of this acute phase were eligible to receive weekly infusions for 4 more weeks in a continuation phase. Acceptability, tolerability, and safety, including adverse and serious adverse events (AEs and SAEs), blood pressure changes, dissociation, craving, in addition to rates of depression response and remission were evaluated. The NIH Toolbox Cognitive Battery was used to assess specific measures of executive function (EF) and overall fluid cognition. RESULTS: Completion rates were 88% for the acute phase and 100% for the continuation phase. No AEs resulted in participant discontinuation, and there were no SAEs. Treatment-emergent elevation of blood pressure, dissociation, and craving were transient and did not result in any participant discontinuation. Depressive symptoms improved significantly and 48% of participants responded. During the acute phase, the EF measures and the fluid cognition composite score improved (Cohen's d = 0.61), and these improvements were sustained in the continuation phase. CONCLUSION: This pilot study suggests that repeated IV ketamine infusions are well-tolerated and are associated with improvement in depression and EF in older adults with TRD. These promising findings need to be confirmed and extended in a larger randomized controlled trial.

A digital health intervention to stabilize the 24-hour rhythm of sleep, meals, and physical activity for reducing depression among older bereaved spouses: Protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence of depression and disruption to 24-h sleep-wake routines following the death of a spouse in late-life, no bereavement interventions have been developed to re-entrain a regular sleep-wake routine among older widow(er)s. We describe the rationale and methodology of the NIH-funded WELL Study (Widowed Elders' Lifestyle after Loss), a randomized controlled trial (RCT) comparing the efficacy of a digital health intervention (DHI) to enhanced usual care (EUC) arm for reducing depression symptoms in older spousally-bereaved adults. METHODS: We will randomize approximately 200 recently bereaved (<12 months) adults aged 60+ years to one of two 12-week interventions: digital monitoring of the timing and regularity of sleep, meals, and physical activity plus weekly motivational health coaching; or enhanced usual care consisting of weekly telephone calls and similar assessment schedules. Participants will complete self-report and clinical assessments at baseline, post-intervention, and 3-, 6-, and 12-months post-intervention, and objective actigraphic assessments of their 24-h rest-activity rhythm (RAR) at baseline and 1-, 2-, and 3-months during the intervention. The primary outcome is change in depression symptoms burden (using the Hamilton Rating Scale for Depression) from pre- to post-intervention and over 12 months of follow-up. DISCUSSION: WELL Study findings will inform the development of widely generalizable and scalable technology-based interventions to support bereaved spouses in community-based settings. Clinical http://Trials.gov Identifier: NCT04016896.

Predicting Medication Nonadherence in Older Adults With Difficult-to-Treat Depression in the IRL-GRey Randomized Controlled Trial.

OBJECTIVE: Nonadherence to antidepressants interferes with optimal treatment of late-life depression. This analysis examines clinical and treatment factors predicting medication nonadherence in difficult-to-treat late-life depression. METHODS: Secondary analysis of data from a clinical trial of antidepressant pharmacotherapy for Major Depressive Disorder in 468 adults aged 60+ years. All participants received venlafaxine XR for 12 weeks. Nonremitters were randomized to augmentation with either aripiprazole or placebo for 12 additional weeks. Medication adherence was assessed 14 times over 24 weeks. The analyses examined sociodemographic, clinical, and treatment factors that may predict antidepressant nonadherence during early (weeks 1-6), late (weeks 7-12), and augmentation (weeks 13--24) treatment. RESULTS: Poor cognitive function and early response were predictive of early nonadherence. Poor cognitive function and prior nonadherence were predictive of late nonadherence. Living alone was associated with nonadherence both late and during augmentation treatment. CONCLUSION: Future studies should consider the role of early response and cognitive function to improve antidepressant adherence, particularly among older adults who live alone.

A systematic review of community pharmacy initiatives to improve treatment of depression and pain: Focus on types of programs and patient-reported outcomes.

INTRODUCTION: Depression and pain are common, disabling, mutually exacerbating conditions. Many patients living with these conditions present to community pharmacies on a regular schedule to purchase both prescribed and over-the-counter medications. Community-pharmacy based programs have been developed to improve depression and pain outcomes. METHODS: The PRISMA guidelines were utilized to answer the following question: In patients with depression and/or pain, what is the effect of the existing community pharmacy programs on depression and/or pain outcomes. Queried databases included Pubmed, EMBASE, and PsychINFO. DistillerSR was used to organize the screening, abstraction, and review of data. All potential articles were evaluated by two authors, and conflicts were discussed to achieve resolution. In addition to primary outcomes, sources of potential bias and quality indicators were abstracted for every article. RESULTS: Three thousand nine hundred and twenty articles were reviewed, and 13 studies met eligibility criteria (n = 7 for depression; n = 6 for pain). Most studies demonstrated improvement in measures of depression or pain. However, compared to usual care or other control conditions, most of the depression and pain-specific interventions did not provide additional symptomatic benefit. The community pharmacy-based interventions were superior for other outcomes including medication adherence, reducing stigma, improvement in self-efficacy, and improvement in general management of disease. CONCLUSION: Community pharmacies may be uniquely positioned to deliver interventions that improve outcomes associated with successful depression and pain treatment outcomes. However, the benefits of published community pharmacy-based treatments for actually improving depression and pain severity has not yet been established. Innovative interventions and additional research may be needed to achieve clinical success for pharmacy interventions for depression and pain.

Coprescribed Benzodiazepines in Older Adults Receiving Antidepressants for Anxiety and Depressive Disorders: Association With Treatment Outcomes.

OBJECTIVE: There is a paucity of data on the effects of coprescribed benzodiazepines on treatment response variability and adherence to antidepressant pharmacotherapy for depression and anxiety in late life. The objective of this transdiagnostic analysis was to examine the effect of benzodiazepines on treatment outcomes in older patients with generalized anxiety disorder (GAD) or major depressive disorder (MDD). METHODS: Secondary analyses of data from 2 clinical trials of antidepressant pharmacotherapy for GAD (escitalopram vs placebo, 2006-2009) or MDD (open treatment with venlafaxine, 2009-2014) were conducted. Participants included 640 adults aged 60+ years with DSM-IV-defined GAD (n = 177) or MDD (n = 463). Benzodiazepine data were collected at baseline. Adherence and treatment response were assessed over 12 weeks. The analysis addressed whether coprescribed benzodiazepines are associated with treatment response, antidepressant medication adherence, dropout, final dose of antidepressant medication, and report of antidepressant-related adverse effects. RESULTS: Participants with GAD and coprescribed benzodiazepines were treated with a lower mean dosage of escitalopram and were less likely to complete the trial; there was no difference in adherence or treatment response. Participants with MDD and coprescribed benzodiazepines were less likely to tolerate a therapeutic dose of venlafaxine and reported more medication-related adverse effects; there was no difference in adherence, dropout, or treatment response. CONCLUSIONS: Coprescription of benzodiazepines was associated with increased dropout in older patients with GAD and more medication-related adverse effects in older patients with MDD. However, with the systematic clinical attention offered in a clinical trial, they do not impede treatment response. Clinicians should be aware that a coprescribed benzodiazepine may be a marker of a more challenging treatment course. Trial Registration: Data analyzed were from studies with ClinicalTrials.gov identifiers NCT00892047 and NCT00105586.

Engaging in Late-Life Mental Health Research: a Narrative Review of Challenges to Participation.

PURPOSE OF REVIEW: This narrative review seeks to ascertain the challenges older patients face with participation in mental health clinical research studies and suggests creative strategies to minimize these obstacles. RECENT FINDINGS: Challenges to older adults' engagement in mental health research include practical, institutional, and collaboration-related barriers applicable to all clinical trials as well as more personal, cultural, and age-related patient barriers specific to geriatric mental health research. Universal research challenges include (1) institutional barriers of lack of funding and researchers, inter-researcher conflict, and sampling bias; (2) collaboration-related barriers involving miscommunication and clinician concerns; and (3) practical patient barriers such as scheduling issues, financial constraints, and transportation difficulties. Challenges unique to geriatric mental health research include (1) personal barriers such as no perceived need for treatment, prior negative experience, and mistrust of mental health research; (2) cultural barriers involving stigma and lack of bilingual or culturally matched staff; and (3) chronic medical issues and concerns about capacity. SUMMARY: Proposed solutions to these barriers include increased programmatic focus on and funding of geriatric psychiatry research grants, meeting with clinical staff to clarify study protocols and eligibility criteria, and offering transportation for participants. To minimize stigma and mistrust of psychiatric research, studies should devise community outreach efforts, employ culturally competent bilingual staff, and provide patient and family education about the study and general information about promoting mental health.

Illness narratives and preferences for treatment among older veterans living with treatment-resistant depression and insomnia.

BACKGROUND: Despite the prevalence of comorbid late-life treatmentresistant depression (LLTRD) and insomnia in older adults, there is a gap in the literature describing patient factors, such as patients' beliefs about their illnesses and preferences for treatment, that can facilitate recovery. Therefore, we explored the perceptions and treatment preferences of older veterans with LLTRD and insomnia. METHODS: Semi-structured interviews were completed with 11 older veterans. A thematic analysis of the interviews was conducted. RESULTS: Four main themes were identified: 1. Insomnia and medical problems were considered to be significant contributors to depression, which was defined by low mood and anhedonia; 2. "Overthinking" was thought to be a cause of insomnia; 3. Participants' preference for psychotherapy was driven by their past experiences with therapy; and 4. Participants viewed patient education as a facilitator for compliance. CONCLUSIONS: Older veterans with LLTRD and insomnia have a preference for behavioral interventions. However, they lack knowledge about available treatment options, such as behavioral interventions for sleep that can improve both their sleep and mood while being a good fit with their illness narratives, such as "overthinking." There is a need for patient education, which should be offered early and often during treatment.

Bypassing the blues: Insomnia in the depressed post-CABG population.

BACKGROUND: BACKGROUND: Recovery from coronary artery bypass graft (CABG) surgery often is complicated by depression and insomnia, resulting in poorer health-related quality of life and clinical outcomes. We explored the relationships among depression, insomnia, quality of life, and the impact of a collaborative care strategy on reducing insomnia in patients after CABG surgery. METHODS: METHODS: Patients with a Patient Health Questionnaire score ≥10 were randomized to nurse-delivered collaborative care for depression (n = 150) or their physician's usual care (n = 152). A convenience sample of patients without depression (n = 151) served as the control group. Using the Hamilton Depression Rating Scale sleep questions, we created an "insomnia index." RESULTS: RESULTS: At baseline, 63% of participants who were depressed vs 12% of those who were not depressed reported insomnia. Compared with usual care, fewer collaborative care participants reported insomnia at 8 months, and they tended to have a lower insomnia score (insomnia index change score −0.95 and −1.47, respectively; P = .05) with no time-by- randomization interaction, Cohen's d = 0.22 (95% confidence interval, −0.001 to 0.43). Participants with baseline insomnia reported greater improvements in mental health­related quality of life (Medical Outcomes Survey 36-item Short Form Mental Component Summary score; −3.32, P = .02), but insomnia was not a significant moderator of the effect of collaborative care. CONCLUSIONS: CONCLUSIONS: This is the first study to examine the long-term impact on insomnia among post-CABG patients treated for depression. Future collaborative care studies could consider including a therapeutic focus for insomnia.

Brief behavioral treatment for insomnia in older adults with late-life treatment-resistant depression and insomnia: a pilot study.

OBJECTIVE: Brief Behavioral Treatment for Insomnia (BBTI) is an efficacious treatment of insomnia in older adults. Behavioral treatments for insomnia can also improve depression. However, it is unknown if BBTI is feasible or has an effect in patients with insomnia and late-life treatment resistant depression (LLTRD). The aims of this study were two-fold, to test: 1) the feasibility (defined by acceptability and retention rates) of BBTI and 2) the therapeutic potency of BBTI on symptoms of insomnia and depression. METHODS: Eleven older Veterans with LLTRD and insomnia were recruited in a randomized control trial to receive immediate (4-weeks of BBTI followed by 3-weeks of phone call check-ins and a final in-person 8-week assessment) or delayed (3-weeks of treatment as usual [wait-list control] followed by 4-weeks of BBTI and a final in-person 8-week assessment) BBTI. The primary outcome measures included the Patient Health Questionnaire (minus the sleep item) and the Insomnia Severity Index. RESULTS: BBTI was found to be feasible in older Veterans with insomnia and LLTRD; all participants recommended BBTI and retention rates were 90.9%. There was no difference in treatment effect between the immediate BBTI and delayed BBTI groups at week 4. After both groups (immediate and delayed) received BBTI, improvements were seen in both insomnia (d = 1.06) and depression (d = 0.54) scores. CONCLUSIONS: BBTI is a feasible treatment for insomnia in older adults with LLTRD. BBTI may be an effective adjunctive treatment for depression. Larger adequately-powered trials are required to confirm these preliminary findings.

Effect of insomnia treatments on depression: A systematic review and meta-analysis.

BACKGROUND: Insomnia is frequently co-morbid with depression, with a bidirectional relationship between these disorders. There is evidence that insomnia-specific interventions, such as cognitive behavioral therapy for insomnia, may lead to improvements in depression. The purpose of this systematic review and meta-analysis is to determine whether treatment of insomnia leads to improved depression outcomes in individuals with both insomnia and depression. METHODS: We conduct a systematic review and meta-analysis to explore the effect of treatment for insomnia disorder on depression in patients with both disorders. RESULTS: Three thousand eight hundred and fifteen studies were reviewed, and 23 studies met inclusion criteria. Although all of the studies suggested a positive clinical effect of insomnia treatment on depression outcomes, most of the results were not statistically significant. Although the interventions and populations were highly variable, the meta-analysis indicates moderate to large effect size (ES) improvement in depression as measured with the Hamilton Depression Rating Scale (ES = -1.29, 95%CI [-2.11, -0.47]) and Beck Depression Inventory (ES = -0.68, 95%CI [-1.29, -0.06]). CONCLUSIONS: These results support that treating insomnia in patients with depression has a positive effect on mood. Future trials are needed to identify the subtypes of patients whose depression improves during treatment with insomnia-specific interventions, and to identify the mechanisms by which treating insomnia improves mood.

The role of late life depressive symptoms on the trajectories of insomnia symptoms during antidepressant treatment.

OBJECTIVE: Sleep disturbances are common in late life depression; however, changes in insomnia symptoms during antidepressant treatment need to be characterized further. The objective of this study was two-fold: 1) to describe longitudinal trajectories of insomnia symptoms in older adults receiving antidepressant treatment and 2) to examine whether baseline depressive symptoms were associated with trajectories of sleep over time. METHODS: Data was obtained from 680 older adults (aged ≥ 60) with major depression who participated in one of two protocolized open-label antidepressant treatment clinical trials (Maintenance Therapies in Late Life Depression [MTLD-3]; Incomplete Response in Late Life Depression: Getting to Remission [IRL-GRey]). Depression (total score minus sleep items) and sleep (sum of sleep items) outcomes were derived from the Hamilton Depression Rating Scale in the MLTD-3 and Montgomery-Asberg Depression Rating Scale in the IRL-GRey. RESULTS: Both datasets identified 5 possible trajectories of insomnia symptoms with about half of the older adults having clinically significant baseline sleep disturbances and minimal improvement following a course of antidepressant treatment (i.e., sub-optimal sleep trajectory). Furthermore, across both datasets, worse baseline depression severity was associated with sub-optimal sleep trajectories. CONCLUSION: In older adults receiving antidepressant treatment, those with clinically significant baseline sleep disturbances and greater depression severity may require adjunctive sleep-focused treatment to ameliorate sleep symptoms.

Specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression.

OBJECTIVE: To identify which specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression. METHODS: This is a secondary analysis of data from a late-life treatment resistant depression trial examining the safety and efficacy of aripiprazole augmentation. Participants aged 60 and above were randomized to aripiprazole augmentation (N = 91) versus placebo (N = 90). The main outcome was depression remission. Clinical predictors included individual Montgomery-Asberg Depression Rating Scale (MADRS) item scores categorized as symptomatic (scores >2) or nonsymptomatic (scores ≤2). RESULTS: Three MADRS items predicted depression remission with aripiprazole augmentation: symptomatic scores on sleep disturbance and nonsymptomatic scores on apparent sadness and inability to feel. The 2-way and 3-way interaction terms of these MADRS items were not significant predictors of remission; therefore, the models' ability to predict remission was not improved by combining the significant MADRS items. CONCLUSIONS: The identification of specific depressive symptoms, which can be clinically assessed, can be used to inform treatment decisions. Older adults with treatment resistant depression that present with sleep disturbances, lack of apparent sadness, or lack of inability to feel should be considered for aripiprazole augmentation.

Subjective-Objective Sleep Discrepancy in Older Adults With MCI and Subsyndromal Depression.

BACKGROUND/OBJECTIVES: We investigated the prevalence and correlates of discrepancies between self-reported sleep quality (Pittsburgh Sleep Quality Index) and objective sleep efficiency (actigraphy) in older adults with mild cognitive impairment (MCI) and subsyndromal depression. METHODS: This was a secondary analysis of a clincial trial with 59 adults aged 60 years and older with MCI and subsyndromal depression. We included baseline data on participants' subjective sleep quality, objective sleep efficiency, depressive symptoms, insomnia diagnosis, and cognitive functioning. RESULTS: Pittsburgh Sleep Quality Index subjective sleep quality and actigraphy-measured sleep efficiency were not significantly correlated ( r = -.06; P = .64), with 61% of participants having subjective-objective sleep discrepancies. Correlates of subjective-objective sleep discrepancy included the presence of an insomnia diagnosis and impaired memory, particularly delayed memory. CONCLUSION: These findings are important because subjective underestimation of symptoms in older adults with memory impairments may result in sleep disturbances going unrecognized in clinical practice; on the other hand, an insomnia disorder may be a possible remediable contribution to subjective overestimation of sleep disturbances.