Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.

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

Back Pain Consortium (BACPAC): Protocol and Pilot Study Results for a Randomized Comparative-Effectiveness Trial of Antidepressants, Fear Avoidance Rehabilitation, or the Combination for Chronic Low Back Pain and Comorbid High Negative Affect.

OBJECTIVE: Patients with chronic low back pain (CLBP) and comorbid depression or anxiety disorders are highly prevalent. Negative affect (NA) refers to a combination of negative thoughts, emotions, and behaviors. Patients with CLBP with high NA have greater pain, worse treatment outcomes, and greater prescription opioid misuse. We present the protocol for SYNNAPTIC (SYNergizing Negative Affect & Pain Treatment In Chronic pain). DESIGN: A randomized comparative-effectiveness study of antidepressants, fear-avoidance rehabilitation, or their combination in 300 patients with CLBP with high NA. In the antidepressant- or rehabilitation-only arms, SYNNAPTIC includes an adaptive design of re-randomization after 4 months for nonresponders. SETTING: A multisite trial conducted in routine pain clinical treatment settings: pain clinics and physical and occupational therapy treatment centers. METHODS: Inclusion criteria include CLBP with elevated depression and anxiety symptoms. Antidepressant and rehabilitation treatments follow validated and effective protocols for musculoskeletal pain in patients with high NA. Power and sample size are based on superior outcomes of combination therapy with these same treatments in a 71-subject 4-arm pilot randomized controlled trial. CONCLUSIONS: SYNNAPTIC addresses the lack of evidence-based protocols for the treatment of the vulnerable subgroup of patients with CLBP and high NA. We hypothesize that combination therapy of antidepressants plus fear-avoidance rehabilitation will be more effective than each treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04747314.

Subjective Sleep Quality and Trajectories of Interleukin-6 in Older Adults.

BACKGROUND: We aimed to identify trajectories of inflammation in older adults at elevated risk for syndromal depression and anxiety and to determine whether baseline physical, cognitive, and psychosocial factors could distinguish 15-month longitudinal trajectories. METHODS: Older adults (N = 195, mean age (±SD) = 74.4 years (9.0) participating in three depression and anxiety prevention protocols completed a comprehensive battery of psychosocial assessments and provided blood samples for analysis of interleukin-6 (IL-6) every 3 months over a maximum of 15 months. Group-based trajectory modeling identified trajectories. Adjusted logistic regression examined associations between baseline factors and trajectory groups. RESULTS: Two 15-month trajectories were identified: stable lower IL-6 levels (84%; mean (±SD) = 3.2 (2.1) pg/mL); and consistently higher IL-6 levels (16%; mean = 9.5 (7.4) pg/mL). Poor sleep quality predicted consistently higher levels of IL-6 (OR = 1.9, 95% CI = 1.03-3.55). CONCLUSION: Poor sleep quality may represent a therapeutic target to reduce inflammation.

Care Transitions in the Psychiatric Hospital: Focus on Older Adults.

Patients undergoing a care transition are vulnerable to duplication of services, conflicting care recommendations, and errors in medication reconciliation. Older adults may be more vulnerable to care transitions given their relatively higher medical burden, cognitive impairment, and frequent polypharmacy. In this Treatment in Geriatric Mental Health: Research in Action article, we first present the results of a quality improvement study examining the frequency of care transitions to and from the medical hospital among patients admitted to a university-affiliated psychiatric hospital. Among a sample of 50 geriatric adults and 50 nongeriatric adults admitted to the psychiatric hospital, we tallied the number of care transitions to and from the medical hospital. We found that the geriatric cohort was significantly more likely to experience this type of care transition (p = 0.012, Fisher's exact test) compared to the nongeriatric cohort. In the second part of this article, we use a clinical vignette to illustrate the types of medical errors that can occur as a vulnerable and frail older adult moves between acute psychiatric and medical settings. Finally, we list provider-level and systems-level evidence-based recommendations for how care of the patient in the vignette could be improved. The quality improvement study and clinical vignette demonstrate how older adults are at greater risk for care transitions to and from the acute medical setting during psychiatric hospitalization, and that creative solutions are required to improve outcomes.

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.

Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM): Study Design and Treatment Characteristics of the First 396 Participants Randomized.

OBJECTIVE: Evidence from clinical trials comparing effectiveness and safety of pharmacological strategies in older adults unresponsive to first-line antidepressants is limited. The study, Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM), tests three hypotheses concerning pharmacotherapy strategies for treatment-resistant late-life depression: 1) augmentation strategies will provide greater improvement than switching monotherapies; 2) augmentation strategies will have lower tolerability and more safety concerns than switching monotherapies; and 3) age will moderate the effectiveness and safety differences between treatment strategies. The authors describe the methodology, processes for stakeholder engagement, challenges, and lessons learned in the early phases of OPTIMUM. METHODS: This pragmatic randomized clinical trial located in five North American regions will enroll 1,500 participants aged 60 years and older unresponsive to two or more antidepressant trials. The authors evaluate two strategies (medication augmentation versus switch) using four medications (aripiprazole, bupropion, lithium, and nortriptyline) via a stepwise, prespecified protocol. Primary outcomes include: 1) symptom remission (Montgomery Asberg Depression scale ≤10); 2) psychological well-being, comprising positive affect, general life satisfaction, and purpose; and 3) safety (rates of serious adverse events and prevalence of falls and fall-related injuries). RESULTS: To date, 396 participants have been randomized. The authors report on four challenges: 1) engagement and recruitment; 2) increasing polypharmacy in older adults, resulting in potentially hazardous scenarios; 3) reporting adverse events and procedure standardization across sites; and 4) dissemination of results. CONCLUSION: Solutions to these challenges, including early inclusion of stake holders, will inform future pragmatic studies in older adults with depression.

Clinical and neuropsychiatric correlates of lumbar spinal surgery in older adults: results of a pilot study.

AIM: To improve selection of older lumbar surgical candidates, we surveyed correlates of functioning and satisfaction with surgery. MATERIALS & METHODS: Prospective sample at lumbar spine surgery clinic. Patients (n = 48) were evaluated before surgery and after 3 months. Dependent variables were functioning and surgical satisfaction. RESULTS: Baseline variables associated with disability at 3 months included cognitive status and widespread pain. There was clinically significant improvement with moderate effects sizes for anxiety and depression at follow-up. Patients with at least a 30% improvement in disability had better physical health-related quality of life and were less likely to report widespread pain before surgery. CONCLUSION: Although preliminary, two novel potential predictors of lumbar surgery outcome include diminished cognitive functioning and widespread pain. Further study of these variables on post-surgical functioning and satisfaction may improve patient selection.

Deconstructing chronic low back pain in the older adult--Step by step evidence and expert-based recommendations for evaluation and treatment part III: Fibromyalgia syndrome.

OBJECTIVE: To present the third in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of 12 important contributors to pain and disability in older adults with CLBP. This article focuses on fibromyalgia syndrome (FMS). METHODS: A modified Delphi approach was used to create the evaluation and treatment algorithm, the table discussing the rationale behind each of the algorithm components, and the stepped-care drug recommendations. The team involved in the creation of these materials consisted of a principal investigator, a 5-member content expert panel, and a 9-member primary care panel. The evaluation and treatment recommendations were based on availability of medications and other resources within the Veterans Health Administration (VHA) facilities. However, non-VHA panelists were also involved in the development of these materials, which can be applied to both VA and civilian settings. The illustrative clinical case was taken from the clinical practice of the principal investigator. RESULTS: Following expert consultations and a review of the literature, we developed an evaluation and treatment algorithm with supporting materials to aid in the care of older adults with CLBP who have concomitant FMS. A case is presented that demonstrates the complexity of pain evaluation and management in older patients with CLBP and concomitant FMS. CONCLUSIONS: Recognition of FMS as a common contributor to CLBP in older adults and initiating treatment targeting both FMS and CLBP may lead to improved outcomes in pain and disability.

Advancing the screening of fibromyalgia in late-life depression: practical implications for psychiatric settings.

BACKGROUND: Fibromyalgia (FM) is common in older adults suffering from mood disorders. However, clinical diagnosis of FM is challenging, particularly in psychiatric settings. We examined the prevalence of FM and the sensitivity of three simple screeners for FM. METHODS: Using cross-sectional data, we evaluated three tests against the American College of Rheumatology (ACR) 1990 Criteria for the Classification of FM: a "Do you often feel like you hurt all over?" question, a pain map score, and the Pope and Hudson (PH) interview for FM. Participants were 185 community-dwelling adults ≥ 60 years old with comorbid depression and chronic low back pain evaluated at a late-life mental health clinic. RESULTS: Fifty three of 185 participants (29%) met the ACR 1990 FM criteria. Compared to those without FM, the FM group had more "yes" answers to the "hurt all over?" question and higher pain map scores. To reach a sensitivity of at least 0.90, the cut-off score for the pain map was 8. The sensitivity of the pain map, "hurt all over?" question, and PH criteria were 0.92 [95%CI 0.82-0.98], 0.91 [95%CI 0.79-0.97], and 0.94 [95%CI 0.843-0.99] respectively. CONCLUSIONS: Nearly one in three older adults suffering from depression and chronic low back pain met ACR 1990 FM criteria. Three short screening tests showed high sensitivity when compared to the ACR 1990 FM criteria. Implementation of one of the simple screeners for FM in geriatric psychiatry settings may guide the need for further diagnostic evaluation.

Clinical and demographic covariates of chronic opioid and non-opioid analgesic use in rural-dwelling older adults: the MoVIES project.

BACKGROUND: To describe covariates and patterns of late-life analgesic use in the rural, population-based MoVIES cohort from 1989 to 2002. METHODS: Secondary analysis of epidemiologic survey of elderly people conducted over six biennial assessment waves. Potential covariates of analgesic use included age, gender, depression, sleep, arthritis, smoking, alcohol, and general health status. Of the original cohort of 1,681, this sample comprised 1,109 individuals with complete data on all assessments. Using trajectory analysis, participants were characterized as chronic or non-chronic users of opioid and non-opioid analgesics. Multivariable regression was used to model predictors of chronic analgesic use. RESULTS: The cohort was followed for mean (SD) 7.3 (2.7) years. Chronic use of opioid analgesics was reported by 7.2%, while non-opioid use was reported by 46.1%. In the multivariable model, predictors of chronic use of both opioid and non-opioid analgesics included female sex, taking ≥2 prescription medications, and "arthritis" diagnoses. Chronic opioid use was also associated with age 75-84 years; chronic non-opioid use was also associated with sleep continuity disturbance. CONCLUSIONS: These epidemiological data confirm clinical observations and generate hypotheses for further testing. Future studies should investigate whether addressing sleep problems might lead to decreased use of non-opioid analgesics and possibly enhanced pain management.

The impact of pain and depression on recovery after coronary artery bypass grafting.

OBJECTIVE: To describe the relationship between pain and depression on recovery after coronary artery bypass grafting (CABG). METHODS: A secondary data analysis on 453 depressed and nondepressed post-CABG patients enrolled in a randomized, controlled, effectiveness trial of telephone-delivered collaborative care for depression. Outcome measures were collected from March 2004 to September 2007 and included pain, physical function, and mood symptoms. RESULTS: Depressed patients (baseline Patient Health Questionnaire-9 score ≥10) versus those without depression reported significantly worse pain scores on the 36-Item Short Form Health Survey Bodily Pain Scale at baseline and up to 12 months post-CABG, p < .05. Among patients with depression, those who received collaborative care reported significantly better pain scores at each time point between 2 and 12 months post-CABG versus depressed patients randomized to the usual care control group, p < .05. Regardless of intervention status, depressed participants with at least moderate pain at baseline reported significantly lower functional status (measured by the Duke Activity Status Index) at 8 and 12 months versus depressed patients with none or mild pain, p < .05. Depressed patients with at least moderate pain at baseline were also significantly less likely to show improvement of depressive symptoms throughout the course of follow-up versus depressed patients with little or no pain, p < .05. These findings controlled for age, gender, education, race, comorbid conditions, and baseline pain diagnosis. CONCLUSIONS: Depression and pain seem to influence functional recovery post-CABG. The relationship between these two conditions and 12-month outcomes should be considered by clinicians when planning treatment.