Recent research has linked age-related hearing loss to impaired performance across cognitive domains and increased risk for dementia diagnosis. The data linking hearing impairment to incident late-life depression are more mixed but suggest that diminished hearing does increase risk for depression. Behavioral mechanisms may explain these associations, such as the withdrawal of older adults from situations in which they may have difficulty hearing and communicating, which may contribute to the development of social isolation, loneliness, and consequent cognitive decline and depression. At a neural level, chronic hearing loss leads to reduced activation in central auditory pathways, resulting in compensatory increased activation in the cognitive control network, dysfunctional auditory–limbic connectivity, and deafferentation-induced atrophy in frontal brain regions. These pathologic changes decrease cognitive performance and increase depression risk by reducing cognitive reserve, increasing executive dysfunction, and disrupting normative emotion reactivity and regulation. Based on the available data and informed by this model, evidence-based suggestions are proposed for clinicians treating older adults, and a research agenda is advanced to facilitate the development of rationally designed and age-appropriate psychiatric treatments for older adults with age-related hearing loss. First and foremost, treating hearing loss should be investigated as a means of improving cognitive and depressive outcomes in well-designed studies incorporating comprehensive psychiatric assessments, randomization, objective documentation of compliance, and analyses of treatment mediators that will facilitate further therapeutic development. Multimodal neuroimaging studies integrating audiometric, neuropsychological, and clinical assessments also are needed to further evaluate the model proposed.
Placebo response in clinical trials of antidepressant medications is substantial and increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to more failed trials and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for Major Depressive Disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. This review examines contributors to placebo response in antidepressant clinical trials and proposes an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact that enhances treatment response.
Context.-Depression and ischemic heart disease often are comorbid conditions and, in patients who have had a myocardial infarction, the presence of depression is associated with increased mortality. Patients with heart disease need a safe and effective treatment for depression. Objective.-To compare the efficacy, cardiovascular effects, and safety of a specific serotonin reuptake inhibitor, paroxetine, with a tricyclic antidepressant, nortriptyline hydrochloride, in depressed patients with ischemic heart disease. Design.-Two-week placebo lead-in followed by a double-blind randomized 6week medication trial. Setting.-Research clinics in 4 university centers. Patients.-Eighty-one outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder and with documented ischemic heart disease. Interventions.-Treatment with either paroxetine, 20 to 30 mg/d, or nortriptyline targeted to a therapeutic plasma level, 190 to 570 nmol/L (50-150 ng/mL), for 6 weeks. Main Outcome Measures.-For effectiveness of treatment, a decline in the score of the Hamilton Rating Scale for Depression by 50% and final score of 8 or less; for cardiovascular safety, heart rate and rhythm, supine and standing systolic and diastolic blood pressures, electrocardiogram conduction intervals, indexes of heart rate variability, and rate of adverse events. Results.-By intent-to-treat analysis, 25 (61%) of 41 patients improved during treatment with paroxetine and 22 (55%) of 40 improved with nortriptyline. Neither drug significantly affected blood pressure or conduction intervals. Paroxetine had no sustained effects on heart rate or rhythm or indexes of heart rate variability, whereas patients treated with nortriptyline had a sustained 11% increase in heart rate from a mean of 75 to 83 beats per minute (PϽ.001) and a reduction in heart rate variability, as measured by the SD of all normal R-R intervals over a 24-hour period, from 112 to 96 (PϽ.01). Adverse cardiac events occurred in 1 (2%) of 41 patients treated with paroxetine and 7 (18%) of 40 patients treated with nortriptyline (PϽ.03). Conclusions.-Paroxetine and nortriptyline are effective treatments for depressed patients with ischemic heart disease. Nortriptyline treatment was associated with a significantly higher rate of serious adverse cardiac events compared with paroxetine.
To determine the effect of the COVID-19 pandemic on the mental health of older adults with pre-existing major depressive disorder (MDD). Participants: Participants were 73 community-living older adults with pre-existing MDD (mean age 69 [SD 6]) in Los Angeles, New York, Pittsburgh, and St Louis. Design and Measurements: During the first 2 months of the pandemic, the authors interviewed participants with a semistructured qualitative interview evaluating access to care, mental health, quality of life, and coping. The authors also assessed depression, anxiety, and suicidality with validated scales and compared scores before and during the pandemic. Results: Five themes from the interviews highlight the experience of older adults with MDD: 1) They are more concerned about the risk of contracting the virus than the risks of isolation. 2) They exhibit resilience to the stress and isolation of physical distancing. 3) Most are not isolated socially, with virtual contact with friends and family. 4) Their quality of life is lower, and they worry their mental health will suffer with continued physical distancing. 5) They are outraged by an inadequate governmental response to the pandemic. Depression, anxiety, and suicidal ideation symptom scores did not differ
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