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.

Association between increased theta cordance and early response to ECT in late-life depression.

OBJECTIVES: More than half of patients with major depression who do not respond to initial antidepressants become treatment resistant (TRD), and while electroconvulsive therapy (ECT) is effective, it involves anesthesia and other medical risks that are of concern in geriatric patients. Past studies have suggested that theta cordance (TC), a correlate of cerebral metabolism measured by electroencephalography, could guide treatment decisions related to patient selection and engagement of the therapeutic target. METHODS/DESIGN: Eight patients with late-life treatment resistant depression (LL-TRD) underwent magnetoencephalography (MEG) at baseline and following seven sessions of ECT. We tested whether the mean and regional frontal cortex TC were able to differentiate early responders from nonresponders. RESULTS: Five patients whose depression severity decreased by >30% after seven sessions were considered early responders. We found no baseline differences in mean frontal TC between early responders compared with nonresponders, but early responders exhibited a significant increase in TC following ECT. Further, we found that compared with nonresponders, early responders exhibited a greater change in TC specifically within the right prefrontal cortex. CONCLUSIONS: These results support the hypothesis that increases in frontal TC are associated with antidepressant response. We expand on previous findings by showing that this change is specific to the right prefrontal cortex. Validation of this neural marker could contribute to improved ECT outcomes, by informing early clinical decisions about the acute efficacy of this treatment.

Trajectory of Disability in Older Adults With Newly Diagnosed Diabetes: Role of Elevated Depressive Symptoms.

OBJECTIVE: We examined whether the trajectory of disability differed between older adults with and without elevated depressive symptoms before and after the onset of diabetes mellitus (DM) over 10 years (2004-2014) and explored difficulties in basic and instrumental activities of daily living between the two groups. RESEARCH DESIGN AND METHODS: A generalized linear mixed-model analysis was conducted using five waves (8th-12th) of Health and Retirement Study (HRS) data. We included 419 older adults who self-reported new DM diagnosis within the previous 2 years and used the Center of Epidemiologic Studies Depression Scale to measure elevated depressive symptoms. Disability was measured by 10 items defined in the HRS data set. RESULTS: The trajectory of disability differed between older adults with and without elevated depressive symptoms after newly diagnosed DM over time. Significant and clinically meaningful between-group differences were found in disability after the onset of DM (waves 10 and 11) but not before the onset of DM (waves 8 and 9). Among older adults with elevated depressive symptoms, disability at pre-DM waves (8 and 9) was significantly less than post-DM waves (10-12). Difficulties with shopping, walking, and dressing were mostly reported by older adults with elevated depressive symptoms. CONCLUSIONS: Older adults with newly diagnosed DM and elevated depressive symptoms have a clinically meaningful and faster disablement trajectory than those without elevated depressive symptoms. Future interventions may take an indicated approach to disability prevention in older adults with newly diagnosed DM, especially in those with a change in depression severity.

A Systematic Review of Opioid and Benzodiazepine Misuse in Older Adults.

OBJECTIVE: The authors assessed the prevalence of opioid and benzodiazepine prescription drug misuse in older adults, the risk factors associated with misuse, and age-appropriate interventions. METHODS: Following PRISMA guidelines, a literature search of PubMed, PsycINFO, and EMBASE for peer-reviewed journal articles in English through April 2014 with updates through November 2015 was conducted for reports on misuse of prescription benzodiazepines and opioids in older adults. Relevant publications were reviewed that included participants age ≥65 years. Reference lists were manually searched for key identified articles and geriatric journals through April 2016. Information on the study design, sample, intervention, comparators, outcome, time frame, and risk of bias were abstracted for each article. RESULTS: Of 4,932 reviewed reports, 15 were included in this systematic review. Thirteen studies assessed the prevalence of prescription drug misuse and included studies related to opioid shopping behavior, assessment of morbidity and mortality associated with opioid and/or benzodiazepine use, frequency and characteristics of opioid prescribing, frequency of substance use disorders and nonprescription use of pain relievers, and health conditions and experiences of long-term benzodiazepine users. One study identified risk factors for misuse, and one study described the effects of provider education and an electronic support tool as an intervention. CONCLUSION: There is a dearth of high quality research on prescription drug misuse in older adults. Existing studies are heterogeneous, making it difficult to draw broad conclusions. The need for further research specific to prescription drug misuse among older adults is discussed.

Design and Implementation of an Intervention Development Study: Retaining Cognition While Avoiding Late-Life Depression (ReCALL).

OBJECTIVE: To discuss the design, rationale, and implementation of an intervention development study addressing indicated and selective prevention of depression and anxiety in individuals 60 years and older with mild cognitive impairment (MCI) and in their caregivers. METHODS: In Phase I, now completed, we developed and standardized problem-solving therapy (PST) and the combined PST + moderate-intensity physical exercise (PE) intervention to be administered to participants with MCI and their caregivers together, dyadically, with both participants working with the same interventionist in the same therapy sessions. In Phase II we have been testing the interventions against enhanced usual care (EUC) and have addressed challenges to recruitment. Randomization was to one of three cells: PST + PE, PST, or EUC. RESULTS: Although we set out to intervene dyadically, many individuals with MCI lived alone or did not have a support person who could participate in the study with them. Consequently, we modified the study to include MCI participants with and without support persons. Ninety-four participants were enrolled: 20 with MCI together with their support persons (N = 20 dyads) and 54 MCI participants without accompanying support persons. Most participants have been satisfied with the usefulness of the interventions in managing stress and cognitive problems. CONCLUSION: PST and moderate-intensity PE are acceptable interventions for depression and anxiety prevention in older adults with MCI and their available caregivers.

Challenges and Solutions for Depression Prevention Research: Methodology for a Depression Prevention Trial for Older Adults with Knee Arthritis and Emotional Distress.

OBJECTIVE: To describe the methodology, challenges, and baseline characteristics of a prevention development trial entitled "Reducing Pain, Preventing Depression." METHODS: A sequential multiple assignment randomized trial (SMART) compared sequences of cognitive behavioral therapy (CBT) and physical therapy for knee pain and prevention of depression and anxiety. Participants were randomized to CBT, physical therapy, or enhanced usual care and followed for 12 months for new-episode depression or anxiety. Participants were age ≥ 60 with knee osteoarthritis and subsyndromal depression, defined as 9-item Patient Health Questionnaire (PHQ-9) score ≥1 (which included the endorsement of one of the cardinal symptoms of depression [low mood or anhedonia]) and no diagnosis of major depressive disorder per the Structured Clinical Interview for DSM-IV. Depression and anxiety severity and characterization of new episodes were assessed with the PHQ-9, Generalized Anxiety Disorder-7, and the PRIME-MD. Knee pain was characterized with the Western Ontario McMaster Arthritis Index. Response was defined as at least "Very Much Better" on a Patient Global Impression of Change. RESULTS: At baseline there were 99 patients with an average age of 71; 61.62% were women and 81.8% white. The average PHQ-9 was 5.6 and average Generalized Anxiety Disorder-7, was 3.2. Most were satisfied with the interventions and study procedures. The challenges and solutions described here will also be used in a confirmatory clinical trial of efficacy. CONCLUSION: A SMART design for depression and anxiety prevention, using both CBT and physical therapy, appears to be feasible and acceptable to participants. The methodologic innovations of this project may advance the field of late-life depression and anxiety prevention.