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1.  Psychotherapy for subclinical depression: meta-analysis 
The British Journal of Psychiatry  2014;205(4):268-274.
There is controversy about whether psychotherapies are effective in the treatment of subclinical depression, defined by clinically relevant depressive symptoms in the absence of a major depressive disorder.
To examine whether psychotherapies are effective in reducing depressive symptoms, reduce the risk of developing major depressive disorder and have comparable effects to psychological treatment of major depression.
We conducted a meta-analysis of 18 studies comparing a psychological treatment of subclinical depression with a control group.
The target groups, therapies and characteristics of the included studies differed considerably from each other, and the quality of many studies was not optimal. Psychotherapies did have a small to moderate effect on depressive symptoms against care as usual at the post-test assessment (g = 0.35, 95% CI 0.23-0.47; NNT = 5, 95% CI 4-8) and significantly reduced the incidence of major depressive episodes at 6 months (RR = 0.61) and possibly at 12 months (RR = 0.74). The effects were significantly smaller than those of psychotherapy for major depressive disorder and could be accounted for by non-specific effects of treatment.
Psychotherapy may be effective in the treatment of subclinical depression and reduce the incidence of major depression, but more high-quality research is needed.
PMCID: PMC4180844  PMID: 25274315
2.  Depression among older adults with diabetes mellitus 
Clinics in geriatric medicine  2014;31(1):117-137.
Depression is among the leading causes of decreased disability-adjusted life years in the world1 and a serious public health problem.2 Older adults with DM experience greater risk for comorbid depression compared to those who do not have DM.3 Having DM increases the risk of subsequent development or recurrence of depression. Conversely, history of depression increases the risk for new onset DM.4 As an unwanted co-traveler of DM, undetected, untreated or undertreated depression impinges an individual’s ability to manage their DM successfully, hindering their adherence to treatment regime.5 It also undermines the effectiveness of provider-patient communication and decays therapeutic relationships. Thus, in the context of caring for older adults with DM, comorbid depression presents special challenges and opportunities for clinicians. Moreover, recent studies have suggested that co-occurring depression and DM may accelerate cognitive decline, highlighting the importance of treating depression and DM. Several treatment modalities are available, which can be used to treat and manage depression in primary care settings: pharmaceutical, brief psychotherapeutic, behavioral and life style interventions, and combination therapies. An evidence-based health care delivery model is also available for treating depression in primary care settings. In this article, we summarize the clinical presentation of late-life depression, potential mechanisms of comorbidity of depression and DM, importance of depression in the successful management of DM, and available best practice models for depression treatment.
PMCID: PMC4254540  PMID: 25453305
Diabetes; Depression; Mood disorders; Aging; Collaborative Care
3.  Assessing the Relationship between Physical Illness and Mental Health Service Use and Expenditures among Older Adults from Racial/Ethnic Minority Groups 
The association of physical illness and mental health service use in older adults from racial/ethnic minority groups is an important area of study given the mental and physical health disparities and the low use of mental health services in this population. The purpose of this study is to describe the impact of comorbid physical illness on mental health service use and expenditures in older adults; and to evaluate disparities in mental health service use and expenditures among a racially/ethnically diverse sample of older adults with and without comorbid physical illness.
Data were obtained from the Medical Expenditure Panel Survey (years 2004–2011). The sample included 1563 whites, 519 African-Americans, and 642 Latinos and (N=2,724) aged 65+ with probable mental illness. Using two-part generalized linear models, we estimated and compared mental health service use among those with and without a comorbid physical illness.
Mental health service use was greater for older adults with comorbid physical illness compared to those without a comorbid physical illness. Once mental health services were accessed, no differences in mental health expenditures were found. Comorbid physical illness increased the likelihood of mental health service use in older whites and Latinos. However, the presence of a comorbidity did not impact racial/ethnic disparities in mental health service use.
This study highlighted the important role of comorbid physical illness as a potential contributor to using mental health services and suggests intervention strategies to enhance engagement in mental health services by older adults from racial/ethnic minority groups.
PMCID: PMC4490047  PMID: 25772763
comorbidities; mental health service use; disparities; older adults
4.  Grief-Related Panic Symptoms in Complicated Grief 
Journal of affective disorders  2014;170:213-216.
Although Complicated Grief (CG) has been associated with comorbid Panic Disorder (PD), little is known about panic attacks in CG, and whether panic symptoms may be grief-related. The present study examines the presence and impact of grief-related panic symptoms in CG.
Individuals with CG (n=146, 78% women, mean (SD) age =52.4(15.0)) were assessed for CG, DSM-IV diagnoses, work and social impairment, and with the Panic Disorder Severity Scale modified to assess symptoms “related to or triggered by reminders of your loss” and anticipatory worry.
Overall, 39.7% reported at least one full or limited-symptom grief-related panic attack over the past week, and 32.2% reported some level of anticipatory worry about grief-related panic. Of interest, 17% met DSM criteria for PD. Among those without PD, 34.7% reported at least one full or limited-symptom grief-related panic attack over the past week, and this was associated with higher CG symptom severity (t=−2.23, p<0.05), and functional impairment (t=−3.31, p<0.01). Among the full sample, controlling for CG symptom severity and current PD, the presence of at least one full or limited-symptom grief-related panic attack was independently associated with increased functional impairment (B(SE)=4.86(1.7), p<0.01).
Limitations include a lack of assessment of non grief-related panic symptoms and examination of a sample of individuals seeking treatment for CG.
Grief-related panic symptoms may be prevalent among individuals with CG and independently contribute to distress and functional impairment.
PMCID: PMC4252915  PMID: 25254619
grief; bereavement; grief-related panic; panic disorder; functional impairment
5.  The Happy Older Latinos are Active (HOLA) health promotion and prevention study: study protocol for a pilot randomized controlled trial 
Trials  2015;16:579.
Results of previous studies attest to the greater illness burden of common mental disorders (anxiety and depression) in older Latinos and the need for developing preventive interventions that are effective, acceptable, and scalable. Happy Older Latinos are Active (HOLA) is a newly developed intervention that uses a community health worker (CHW) to lead a health promotion program in order to prevent common mental disorders among at-risk older Latinos. This pilot study tests the feasibility and acceptability of delivering HOLA to older, at-risk Latinos.
HOLA is a multi-component, health promotion intervention funded by the National Institute of Mental Health (NIMH). This prevention approach will be tested against a fotonovela, an enhanced psychoeducation control condition, in a sample of Latino elderly with minor or subthreshold depression or anxiety. A total of 60 older Latinos (aged 60+) will be randomized to receive HOLA or the fotonovela. The primary outcomes of interest are recruitment, adherence, retention, and acceptability. Data will also be collected on: preemption of incident and recurrent major depression, generalized anxiety, and social phobia; reduction in depression and anxiety symptom severity; physical functioning; sedentary behaviors; social engagement; and self-efficacy.
The results of this study could have implications for other high-risk, highly disadvantaged populations. The development of a health promotion intervention designed to prevent common mental disorders could be a means of addressing multiple disparities (for example, mental health outcomes, mental health service use, stigma) among racial/ethnic minority elderly. Identifier
NCT02371954. Date of registration: 21 January 2015.
PMCID: PMC4683729  PMID: 26683695
Latinos; Mental illness prevention; Older adults; Health promotion
6.  Neuropsychological Functioning in the Acute and Remitted States of Late-Life Depression 
Late-life depression (major depression occurring in an adult 60 years or older) is a common condition that frequently presents with cognitive impairment. Up to half of individuals with LLD are estimated to have cognitive impairment greater than that of age- and education-matched comparators, with impairments of episodic memory, speed of information processing, executive functioning, and visuospatial ability being most common. To inform our understanding of the state- versus trait-effects of depression on neuropsychological functioning, and to overcome limitations of previous studies, we utilized baseline data from the longitudinal Pathways study to compare differences in single time point performance on a broad-based neuropsychological battery across three diagnostic groups of older adults, each comprised of unique participants (N=438): currently depressed (n=120), previously depressed but currently euthymic (n=190), and never-depressed (n=128). Consistent with our hypotheses, we found that participants with a history of depression (currently or previously depressed) performed significantly worse than never-depressed participants on most tests of global cognition, as well as on tests of episodic memory, attention and processing speed, verbal ability, and visuospatial ability; in general, differences were most pronounced within the domain of attention and processing speed. Contrary to our hypothesis, we did not observe differences in executive performance between the two depression groups, suggesting that certain aspects of executive functioning are “trait deficits” associated with LLD. These findings are in general agreement with the existing literature, and represent an enhancement in methodological rigor over previous studies given the cross-sectional approach that avoids practice effects on test performance.
PMCID: PMC4675725  PMID: 25471193
cognitive function; neuropsychological; depression; elderly; geriatric; assessment
7.  The effects of psychotherapy for adult depression on social support: A meta-analysis 
Cognitive therapy and research  2014;38(6):600-611.
Social support is an important extra-therapeutic context of depression treatment, yet no overall estimate is available on how depression treatment affects social support or the size of such an effect. We conducted a meta-analysis of clinical trials of psychotherapy for depression that reported results for social support at post-treatment. A total of 1,579 adults with depression from 11 trials comparing psychotherapy to care-as-usual or waiting list were included. The majority of these studies assessed the participants’ perceptions of social support. Specifically, three studies targeted women with postpartum depression, and four studies targeted individuals with chronic disease. In all these studies, psychotherapy had a small to moderate, yet consistent effect on social support compared to care-as-usual or waiting list at post-treatment (g = 0.38; 95% CI: 0.29~0.48) and at 3–6 month follow-up (g= 0.38; 95% CI: 0.14~0.63). Little evidence of heterogeneity was found across studies, and the results were consistent in several sensitivity analyses. No significant publication bias was detected (Egger’s test p > 0.1). The result of meta-regression showed that improvement in depression symptoms was associated with improvement in social support, but this was not statistically significant.
PMCID: PMC4465276  PMID: 26085699
8.  Reliability and Validity of the Executive Interview (EXIT) and Quick EXIT among Community Dwelling Older Adults 
To investigate the psychometric properties of the Executive Interview (EXIT) and Quick EXIT in community dwelling older adults.
Secondary analysis of data obtained as part of a longitudinal study of cognitive function in late life depression. Setting: A university hospital.
Community dwelling adults (n=422), aged 59 years and older, with current or recent history of non-psychotic unipolar major depression, and never-depressed comparison subjects.
The EXIT and other measures of executive control functions (ECF), non-executive cognitive domains and global cognitive function. We calculated Quick EXIT scores from the EXIT.
The EXIT demonstrated high inter-rater reliability (Intraclass correlation coefficient = .978, F(7, 21) = 174.85, p < .001), while both the EXIT and Quick EXIT demonstrated moderate internal consistency (α= 0.66 and α = 0.68, respectively). Both tests also demonstrated acceptable convergent validity against several standard tests of ECF (rs −.399 to .322, except for the Trail Making Test B, where rs was .057 to .063) as well as against measures of multifactorial cognitive function (rs −.432 to .491). However, both tests demonstrated inconsistent discriminant validity against a variety of standard non-ECF tests (rs −.013 to .376).
Both the EXIT and the Quick EXIT have adequate reliability and appear to require ECF in this population. However, both the EXIT and the Quick EXIT also reflect non-ECF domains. The EXIT and Quick EXIT should be considered to be measures of global cognitive function rather than pure ECF measures. Given similar reliability and validity, the Quick EXIT should be preferred clinically as it is briefer and less burdensome than the full EXIT.
PMCID: PMC3980173  PMID: 24119860
Executive Functions; Cognition; Aged
9.  Activities and Adaptation in Late-Life Depression: A Qualitative Study 
Interviews with 27 community-dwelling older adults with depression shed light on activity choices of this population and underscore the need for occupational therapy practitioners to complete a client-centered, qualitative assessment to understand why activities are continued or stopped.
OBJECTIVE. We sought to understand activity choices of older adults when they were depressed.
METHOD. Each community-dwelling participant (n = 27) completed one semistructured interview while in recovery for at least 3 mo. but less than 7 mo. Transcripts were coded to identify relevant themes.
RESULTS. Six themes emerged that explained activities participants continued while depressed, and four themes described activities they stopped.
CONCLUSION. Older adults maintained many instrumental activities of daily living while depressed, and some actively adapted activities so they could continue them. Some intentionally stopped activities to direct limited energy to their highest priority activities. To guide effective intervention, it is critical for occupational therapy practitioners to complete a client-centered qualitative assessment to understand what and, most important, why activities are continued or stopped. Each theme for activities continued and activities stopped lends itself to intervention strategies.
PMCID: PMC4153555  PMID: 25184470
activities of daily living; adaptation, psychological; choice behavior; depressive disorder; motivation; qualitative research
10.  Association Between Insomnia Symptoms and Functional Status in U.S. Older Adults 
We studied the association between insomnia symptoms and late-life functioning, including physical capacity, limitations in household activities, and participation in valued activities.
Participants were 6,050 adults independent in self-care activities from a representative sample of older Medicare beneficiaries. They completed objective measures of physical capacity and self-report measures of insomnia symptoms, help and difficulty with household activities, and participation in valued activities.
After adjustment, insomnia symptoms were associated with a greater odds of receiving help or having difficulty with selected household activities (laundry, shopping), greater odds of help or difficulty with ≥1 household activity [1 symptom vs. 0, odds ratio (OR)=1.27, p < .05; 2 symptoms vs. 0, OR = 1.35, p < .01), and of restricted participation in specific valued activities (attending religious services, going out for enjoyment) and in ≥1 valued activity (1 symptom vs. 0, OR = 1.29, p < .05; 2 symptoms vs. 0, OR = 1.50, p < .01). There was no independent association between insomnia symptoms and physical capacity.
Among older adults, insomnia symptoms are associated with a greater odds of limitation in household activities and of restricted participation in valued activities. Insomnia interventions may improve functioning and quality of life among elders.
PMCID: PMC4303065  PMID: 25342821
Function; Insomnia; Sleep; Valued activities.
11.  Cognitive Functioning in Complicated Grief 
Complicated grief (CG) is increasingly recognized as a debilitating outcome of bereavement. Given the intensity of the stressor, its chronicity, and its association with depression, it is important to know the impact CG may have on cognitive functioning. This exploratory and descriptive study examined global and domain-specific cognitive functioning in a help-seeking sample of individuals with CG (n=335) compared to a separately ascertained control sample (n=250). Cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA). Controlling for age, sex and education effects, CG participants had lower total MoCA, visuospatial and attention scores relative to control participants. The two groups did not differ significantly in the domains of executive function, language, memory or orientation. Age, sex, and education accounted for much of the variance in MoCA scores, while CG severity and chronicity accounted for a very small percentage of MoCA score variance. Major depression was not a significant predictor of MoCA scores. This study is consistent with previous work demonstrating lower attention and global cognitive performance in individuals with CG compared to control participants. This study newly identifies the visuospatial domain as a target for future studies investigating cognitive functioning in CG.
PMCID: PMC4163517  PMID: 25088285
12.  Major Depressive Disorder in Older Adults: Benefits and Hazards of Prolonged Treatment 
Drugs & aging  2014;31(9):661-669.
Antidepressants have been shown to reduce the risk of depression recurrence in adults, justifying prolonged antidepressant maintenance therapy for most if not all patients. However, older depressed adults may be at increased risk for antidepressant adverse effects. This article discusses the benefits and hazards of continued treatment in elderly depressed patients, and indicates which patients should and should not receive maintenance phase antidepressants. Most clinical trials conducted so far suggest that prolonged antidepressant use in older adults is efficacious to reduce recurrence rates. The benefits of prolonged antidepressant use may not be restricted to preventing recurrence but also include preservation of overall well-being, social functioning, reduced mortality risk from medical disorders, and reduced risk of dementia. Although generally safe, the prolonged use of antidepressants has been associated with higher risk of osteopenia/osteoporosis (in particular the selective serotonin reuptake inhibitors) and cardiovascular toxicity (tricyclic antidepressants). Fewer data are available for special populations, like those with multiple medical comorbidities or those with dementia; thus, the benefits of prolonged antidepressant use are not clear in these individuals.
PMCID: PMC4615590  PMID: 24989627
13.  Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies 
The British Journal of Psychiatry  2013;202(5):329-335.
Late-life depression may increase the risk of incident dementia, in particular of Alzheimer’s disease and vascular dementia.
To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer’s disease and vascular dementia in individuals with late-life depression in population-based prospective studies.
A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer’s disease and vascular dementia in older adults with late-life depression.
Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer’s disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer’s disease (P = 0.03).
Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer’s disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer’s disease.
PMCID: PMC3640214  PMID: 23637108
14.  Late-life depression in the primary care setting: Challenges, collaborative care, and prevention 
Maturitas  2014;79(2):147-152.
Late-life depression is highly prevalent worldwide. In addition to being a debilitating illness, it is a risk factor for excess morbidity and mortality. Older adults with depression are at risk for dementia, coronary heart disease, stroke, cancer and suicide. Individuals with late-life depression often have significant medical comorbidity and, poor treatment adherence. Furthermore, psychosocial considerations such as gender, ethnicity, stigma and bereavement are necessary to understand the full context of late-life depression.
The fact that most older adults seek treatment for depression in primary care settings led to the development of collaborative care interventions for depression. These interventions have consistently demonstrated clinically meaningful effectiveness in the treatment of late-life depression. We describe three pivotal studies detailing the management of depression in primary care settings in both high and low-income countries. Beyond effectively treating depression, collaborative care models address additional challenges associated with late-life depression. Although depression treatment interventions are effective compared to usual care, they exhibit relatively low remission rates and small to medium effect sizes.
Several studies have demonstrated that depression prevention is possible and most effective in at-risk older adults. Given the relatively modest effects of treatment in averting years lived with disability, preventing late-life depression at the primary care level should be highly prioritized as a matter of health policy.
PMCID: PMC4169311  PMID: 24996484
Late-life depression; Collaborative care; Depression prevention; Treatment of depression; Primary care
15.  Managing depression in older age: psychological interventions 
Maturitas  2014;79(2):160-169.
The number of studies on psychological treatments of depression in older adults has increased considerably in the past years. Therefore, we conducted an updated meta-analysis of these studies. A total of 44 studies comparing psychotherapies to control groups, other therapies or pharmacotherapy could be included. The overall effect size indicating the difference between psychotherapy and control groups was g=0.64 (95% CI: 0.47∼0.80), which corresponds with a NNT of 3. These effects were maintained at 6 months or longer post randomization (g=0.27; 95%CI 0.16∼0.37). Specific types of psychotherapies that were found to be effective included cognitive behavior therapy (g=0.45; 95% CI: 0.29∼0.60), life review therapy (g=0.59; 95% CI: 0.36∼0.82) and problem-solving therapy (g=0.46; 95% CI: 0.18∼0.74). Treatment compared to waiting list control groups resulted in larger effect sizes than treatments compared to care-as-usual and other control groups (p<0.05). Studies with lower quality resulted in higher effect sizes than high-quality studies (p<0.05). Direct comparisons between different types of psychotherapy suggested that cognitive behavior therapy and problem-solving therapy may be more effective than non-directive counseling and other psychotherapies may be less effective than other therapies. This should be considered with caution, however, because of the small number of studies. There were not enough studies to examine the long-term effects of psychotherapies and to compare psychotherapy with pharmacotherapy or combined treatments. We conclude that it is safe to assume that psychological therapies in general are effective in late-life depression, and this is especially well-established for cognitive behavior therapy and problem-solving therapy.
PMCID: PMC4537161  PMID: 24973043
depression; older adults; psychotherapy; cognitive behavior therapy; life review; problem-solving therapy; meta-analysis
16.  The Bypassing the Blues Treatment Protocol: Stepped Collaborative Care for Treating Post-CABG Depression 
Psychosomatic medicine  2009;71(2):217-230.
To present the design of the Bypassing the Blues (BtB) study to examine the impact of a collaborative care strategy for treating depression among patients with cardiac disease. Coronary artery bypass graft (CABG) surgery is one of the most common and costly medical procedures performed in the US. Up to half of post-CABG patients report depressive symptoms, and they are more likely to experience poorer health-related quality of life (HRQoL), worse functional status, continued chest pains, and higher risk of cardiovascular morbidity independent of cardiac status, medical comorbidity, and the extent of bypass surgery.
BtB was designed to enroll 450 post-CABG patients from eight Pittsburgh-area hospitals including: (1) 300 patients who expressed mood symptoms preceding discharge and at 2 weeks post hospitalization (Patient Health Questionnaire (PHQ-9) ≥10); and (2) 150 patients who served as nondepressed controls (PHQ-9 <5). Depressed patients were randomized to either an 8-month course of nurse-delivered telephone-based collaborative care supervised by a psychiatrist and primary care expert, or to their physicians’ “usual care.” The primary hypothesis will test whether the intervention can produce an effect size of ≥0.5 improvement in HRQoL at 8 months post CABG, as measured by the SF-36 Mental Component Summary score. Secondary hypotheses will examine the impact of our intervention on mood symptoms, cardiovascular morbidity, employment, health services utilization, and treatment costs.
Not applicable.
This effectiveness trial will provide crucial information on the impact of a widely generalizable evidence-based collaborative care strategy for treating depressed patients with cardiac disease.
PMCID: PMC4573662  PMID: 19188529
depression; coronary artery bypass surgery; randomized clinical trial; collaborative care; coronary artery disease
17.  The effect of gender, age, and symptom severity in late-life depression on the risk of all-cause mortality: The Bambuí Cohort Study of Aging 
Depression and anxiety  2013;31(9):787-795.
Increased mortality risk and its moderators is an important, but still under recognized, negative outcome of Late-Life Depression (LLD). Therefore, we aimed to evaluate whether LLD is a risk factor for all-cause mortality in a population-based study with over ten years of follow-up, and addressed the moderating effect of gender and symptom severity on mortality risk.
This analysis used data from the Bambuí Cohort Study of Aging. The study population comprised 1.508 (86.5%) of all eligible 1.742 elderly residents. Depressive symptoms were annually evaluated by the GHQ-12, with scores of 5 or higher indicating clinically significant depression. From 1997 to 2007, 441 participants died during 10,648 person-years of follow-up. We estimated the hazard ratio for mortality risk by Cox regression analyses.
Depressive symptoms were a risk factor for all-cause mortality after adjusting for confounding lifestyle and clinical factors (adjusted HR=1.24 CI95% [1.00–1.55], p=0.05). Mortality risk was significantly elevated in men (adjusted HR=1.45 CI95% [1.01 – 2.07], p=0.04), but not in women (adjusted HR=1.13 CI95% [0.84 – 1.48], p=0.15). We observed a significant interaction between gender and depressive symptoms on mortality risk ((HR= 1.72 CI95% [1.18 – 2.49], p=0.004).
The present study provides evidence that LLD is a risk factor for all-cause mortality in the elderly, especially in men. The prevention and adequate treatment of LLD may help to reduce premature disability and death among elders with depressive symptoms.
PMCID: PMC4062606  PMID: 24353128
late-life depression; mortality; cohort study; risk factor
General hospital psychiatry  2014;36(5):453-459.
To determine the 12-month cost-effectiveness of a collaborative care (CC) program for treating depression following coronary artery bypass graft (CABG) surgery versus physicians’ usual care (UC).
We obtained 12 continuous months of Medicare and private medical insurance claims data on 189 patients who screened positive for depression following CABG surgery, met criteria for depression when reassessed by telephone two-weeks following hospitalization (9-item Patient Health Questionnaire ≥10), and were randomized to either an 8-month centralized, nurse-provided, and telephone-delivered collaborative care (CC) intervention for depression or to their physicians’ usual care (UC).
At 12-months following randomization, CC patients had $2,068 lower but statistically similar estimated median costs compared to UC (P=0.30) and a variety of sensitivity analyses produced no significant changes. The incremental cost effectiveness ratio of CC was −$9,889 (−$11,940 to −$7,838) per additional quality-adjusted life-year (QALY), and there was 90% probability it would be cost-effective at the willingness to pay threshold of $20,000 per additional QALY. A bootstrapped cost-effectiveness plane also demonstrated a 68% probability of CC “dominating” UC (more QALYs at lower cost).
Centralized, nurse-provided, and telephone-delivered CC for post-CABG depression is a quality-improving and cost-effective treatment that meets generally accepted criteria for high-value care.
PMCID: PMC4138244  PMID: 24973911
Coronary artery bypass grafting; depression; cost-benefit analysis
19.  Safety, Tolerability, and Clinical Effect of Low-Dose Buprenorphine for Treatment-Resistant Depression in Mid-Life and Older Adults 
The Journal of clinical psychiatry  2014;75(8):e785-e793.
Describe the clinical effect and safety of low-dose buprenorphine, a kappa-opioid receptor antagonist, for treatment-resistant depression (TRD) in mid-life and older adults.
Using an open-label protocol, buprenorphine was prescribed for 15 adults age 50 and older with TRD, diagnosed with the SCID for DSM-IV, between 6/2010-6/2011. The titrated dose of buprenorphine ranged from 0.2 mg-1.6 mg/day. We assessed clinical change in depression, anxiety, sleep, positive and negative affect, and quality of life. Tolerability was assessed by documenting change in vital signs, weight, cognitive function, and side effects. Clinical response durability was assessed 8 weeks after discontinuation of the buprenorphine.
The average dose of buprenorphine was 0.4 mg/day (average maximum dose = 0.7 mg/day). The average depression score (MADRS) at baseline was 27.0 (SD=7.3); and at week 8, 9.5 (SD=9.5). There was a sharp decline in depression severity during the first three weeks of exposure (mean delta=−15.0 (SD=7.9)). Depression-specific items tapping pessimism and sadness improved during exposure, supporting a true antidepressant effect. Treatment emergent side effects (in particular nausea and constipation) were not sustained, vital signs and weight remained stable, and executive function and learning improved from pre- to post-treatment.
Low-dose buprenorphine may be a novel-mechanism medication that provides a rapid and sustained improvement for older adults with TRD. Placebo-controlled trials of longer duration are required to assess efficacy, safety, and physiological and psychological effects of extended exposure to this medication.
PMCID: PMC4157317  PMID: 25191915
20.  Effects of Problem Solving Therapy on Mental Health Outcomes in Family Caregivers of Persons with a New Diagnosis of Mild Cognitive Impairment or Early Dementia: A Randomized Controlled Trial 
Interventions directed at the mental health of family dementia caregivers may have limited impact when focused on caregivers who have provided care for years and report high burden levels. We sought to evaluate the mental health effects of problem-solving therapy (PST), designed for caregivers of individuals with a recent diagnosis of Mild Cognitive Impairment (MCI) or early dementia.
Seventy-three (43 MCI and 30 early dementia) family caregivers were randomly assigned to receive PST or a comparison condition (nutritional education). Depression, anxiety, and problem-solving orientation were assessed at baseline and at 1, 3, 6, and 12 months post intervention.
In general, the PST caregiver intervention was feasible and acceptable to family caregivers of older adults with a new cognitive diagnosis. Relative to nutritional education, PST led to significantly reduced depression symptoms, particularly among early dementia caregivers. PST also lowered caregivers’ anxiety levels, and led to lessening of negative problem orientation.
Enhanced problem-solving skills, learned early after a loved one’s cognitive diagnosis (especially dementia), results in positive mental health outcomes among new family caregivers.
PMCID: PMC4021000  PMID: 24119856
Problem-solving therapy; early family dementia caregiving; early dementia; mild cognitive impairment
21.  Depression, Antidepressants and Bone Health in Older Adults: A Systematic Review 
Some studies have reportedan association between depression or serotonin reuptake inhibitor (SRI) antidepressant use and osteoporosis. This association raises concern about the widespread use of antidepressants in older adults and suggests the need to reevaluate this practice. This review examines the association of both depression and antidepressant use with bone health in older adults and the implications for treatment.
A systematic review of studies of the association between depression or antidepressants and bone health in older adults.
All studies that measured depression or antidepressant exposure and bone mineral density (BMD).
Adults aged 60 and above.
Age, site of BMD measurement by dual-energy x-ray absorptiometry (DXA), measure of depression or depressive symptoms, association between BMD changes and depression or antidepressant use.
Nineteen observational studies met the final inclusion criteria; no experimental studies were found. Several cross-sectional and longitudinal studies found that depression or depressive symptoms were associated with decreased BMD. Few studies and only two longitudinal studies addressed the association between SRI antidepressant use and a decrease in BMD and they had conflicting results.
Depression and depressive symptoms are associated with decreased bone mass and accelerated bone loss in older adults; putative mechanisms underlying this relationship are discussed. There is insufficient evidence that SRI antidepressants adversely affect bone health.Thus, a change in current recommendations for the use of antidepressants in older adults is not justified at the present time. Given the high public health significance of this question, more studies are required to determine whether (and in whom) antidepressants may be deleterious for bone health.
PMCID: PMC4134423  PMID: 25039259
depression; antidepressants; BMD; older adults
22.  Genetic variation in the serotonin transporter and HTR1B receptor predicts reduced bone formation during serotonin reuptake inhibitor treatment in older adults 
Studies have reported an association between serotonin reuptake inhibitors (SRIs) and accelerated bone loss. Genetic variation in the serotonin system might modulate bone metabolism changes during SRI treatment. In a clinical trial we examined functional genetic polymorphisms of serotonin transporter and receptors involved in bone metabolism to determine whether they predict changes in bone metabolism during SRI treatment.
In 69 adults (age ≥ 60) participating in a 12-week, open-label trial of the SRI venlafaxine for major depression, serum markers of bone formation (P1NP) and resorption (β-CTX) were assayed before and after treatment. Participants were genotyped for putative high- versus low-expressing polymorphisms in the serotonin transporter (5HTTLPR) and 1B receptor (HTR1B) genes.
Bone formation was significantly reduced with administration of venlafaxine in participants with the high-expressing 5HTTLPR genotype and those with the low-expressing HTR1B genotype. This primarily occurred in individuals with the combination of the high-expressing 5HTTLPR genotype and the low-expressing HTR1B genotype.
These preliminary findings indicate that genetic variation in the serotonin receptors predicts changes in bone metabolism during SRI use. If these results are replicated and clinically confirmed, we will have identified a genetic subgroup at high risk for deleterious bone outcomes with the use of SRIs.
PMCID: PMC4097941  PMID: 24074042
pharmacogenetics; serotonin; bone diseases; biological markers; aged
23.  Early Intervention to Preempt Major Depression in Older Black and White Adults 
Our objective was to assess the efficacy of Problem Solving Therapy for Primary Care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms in older black and white adults, as compared with an active control condition-- coaching in healthy dietary practices (“DIET”),
247 participants (90 blacks, 154 whites, 3 Asians) with subsyndromal depressive symptoms were recruited into a randomized, “indicated” depression prevention trial comparing effects of PST-PC and DIET on time to episodes of major depressive disorder (SCID/DSM-IV) and level of depressive symptoms (Beck Depression Inventory) over two years. Cumulative intervention time was similar in PST-PC or DIET, averaging 5.5- 6.0 hours in each arm.
PST-PC and DIET did not differ significantly in time to major depressive episodes (HR = .87; p > .748). Participants in both arms experienced low incidence of such episodes (blacks: n=8, 9%; whites n=13, 8%), compared to published rates of one in four or five over one year in persons with subsyndromal symptoms receiving care as usual. Participants also showed a mean decrease of 4 points in depressive symptoms, sustained over two years. Despite greater burden of depression risk factors among blacks, no significant differences with whites were found in the primary outcome
Both PST-PC and DIET are potentially effective in protecting older black and white adults with subsyndromal depressive symptoms from developing episodes of major depression over two years. Absent a control for concurrent usual care, this conclusion is preliminary. If confirmed, both interventions hold promise as scalable, safe, non-stigmatizing interventions for delaying or preventing episodes of major depression in the nation’s increasingly diverse older population.
PMCID: PMC4050338  PMID: 24632760
24.  The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder 
Cognitive impairments are a feature of bipolar disorder (BD) and could be worsened by inflammatory cytokines. We determined whether (i) serum interleukin-1 receptor antagonist (IL-1RA) was increased in elderly BD subjects, (ii) whether IL-1RA was associated with worse neurocognitive function, and (iii) whether IL-1RA was associated with white matter integrity.
21 euthymic BD patients (65 +/− 9 years) with serum available for IL-1RA measures by enzyme-linked immunoassays were compared with 26 similarly aged control participants. Four factor analysis-derived z-scores and a global z-score were obtained from a battery of 21 neurocognitive tests. Diffusion Tensor Images were used to obtain fractional anisotropy (FA), and an Automated Labeling Pathway algorithm was used to obtain white matter hyperintensity (WMH) burden.
IL-1RA was elevated in BD subjects compared to controls (439+/−326 pg/mL vs. 269+/−109 pg/mL; p=0.004). Moreover, IL-1RA was inversely correlated with three cognitive function factors and global cognition (r=−0.37; p=0.01). IL-1RA continued to correlate with global cognitive function even when co-varying for either IL-6 or brain-derived neurotrophic factor (BDNF). Although FA was lower in BD subjects (0.368 +/− 0.02 vs. 0.381 +/− 0.01; p=.02), IL-1RA was not associated with FA or WMH burden.
Elevated serum levels of IL-1RA in BD subjects, even during euthymic states, were associated with worse cognitive function. This association was not explained by co-occurring increases in IL-6, by decreased BDNF, nor by measures of white matter integrity. These cross-sectional findings support the possibility that the IL-1 family may contribute to cognitive impairments in BD.
PMCID: PMC4013203  PMID: 24273017
mood disorder; inflammation; cytokine; cognition; geriatric; white matter; diffusion tensor imaging; fractional anisotropy; white matter hyperintensities
25.  Psychosocial Risk Factors for Cognitive Decline in Late-Life Depression: Findings from the MTLD-III Study 
Canadian Geriatrics Journal  2015;18(2):43-50.
Cognitive impairment and depression frequently co-occur in late life. There remains a need to better characterize psychosocial risk factors of cognitive decline in older adults with depression. We hypothesized that certain psychosocial factors would be associated with higher risk of cognitive decline in individuals with late-life depression.
130 individuals aged ≥ 65 years who had achieved remission from a major depressive episode were randomized to donepezil or placebo and then closely followed for two years. Using Cox proportional hazard models, we examined the association between baseline median household income, education level, race, marital status, and social support and cognitive decline over the follow-up.
Lower interpersonal support (OR = 0.86 [0.74–0.99], p = .04) and lower baseline global neuropsychological score (OR = 0.56 [0.36–0.87], p = .001) predicted shorter time to conversion to MCI or dementia in univariate models. These exposures did not remain significant in multivariate analyses. Neither socioeconomic status nor other psychosocial factors independently predicted cognitive diagnostic conversion (p > .05).
We did not find reliable associations between cognitive outcome and any of the psychosocial factors examined. Future large-scale, epidemiological studies, ideally using well-validated subjective measures, should better characterize psychosocial risk factors for cognitive decline in late-life depression.
PMCID: PMC4487735  PMID: 26180559
psychosocial risk factors; late-life depression; cognition; dementia; mild cognitive impairment; medical illness burden

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