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Biomedical subjects

Charles F Reynolds

Publications and source records attributed to Charles F Reynolds.

At least 37 records · Page 2Linked to original sources

Persistence of neuropsychologic deficits in the remitted state of late-life depression.

OBJECTIVE: Cognitive impairment in late-life depression (LLD) is prevalent, disabling, and persists despite the remission of depressive symptoms. This article characterizes neuropsychologic functioning during remission in LLD. METHODS: The authors examined longitudinal performance on a comprehensive neuropsychologic battery in 56 nondemented subjects age 60 or older who initially presented with an episode of nonpsychotic unipolar major depression and 40 nondemented, age- and education-equated comparison subjects with no history of depression. Subjects were assessed at baseline (in a depressed state) and one year later (when remitted). RESULTS: After one year, 45% of the LLD subjects were cognitively impaired despite remission of depression. Visuospatial ability, information-processing speed, and delayed memory were most frequently impaired; 94% of the patients who were impaired at baseline remained impaired one year later. Twenty-three percent of the patients who were cognitively normal while depressed developed impairment one year later. CONCLUSIONS: Most older individuals who are cognitively impaired during a depressive episode remain impaired when their depression remits. In addition, a substantial proportion of older depressed individuals who are cognitively intact when depressed are likely to be impaired one year later, although their depression has remitted.

Age Factors↗

Cardiovascular changes associated with venlafaxine in the treatment of late-life depression.

BACKGROUND: Potential cardiovascular side effects from venlafaxine-XR must be considered when prescribing this medication, especially in geriatric patients, who often present with comorbid medical conditions. METHODS: Participants age 60 and older with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of a major depressive episode without psychotic features were treated openly with venlafaxine-XR for 12 weeks during which venlafaxine-XR was titrated based on tolerability and response according to predefined guidelines. Sitting and standing blood pressures and heart rates were measured. A 12-lead electrocardiogram was obtained at baseline and at week 12. RESULTS: Sixty-two participants started treatment; 59 completed at least two weeks of the 12-week study. The mean final dose of venlafaxine-XR was 195.5 mg/day (standard deviation: 72.2). Twenty-four percent (95% confidence interval [CI]: 7.3%-40.7%) of initially normotensive participants and 54% (95% CI: 34.3%-74%) of those with preexisting hypertension experienced an increase in blood pressure. Twenty-nine percent (95% CI: 14.6%-43.4%) of participants developed orthostatic hypotension. Two participants experienced a clinically significant increase in QTc interval. One participant reported new-onset mild dizziness, whereas four participants reported new-onset tachycardia or palpitation. Overall, 17 unique participants (28.8%; 95% CI: 17.3%-40.4%) experienced a new-onset cardiovascular problem, potentially related to the study medication. CONCLUSION: Overall, venlafaxine-XR was well tolerated. However, similar to previous reports, venlafaxine-XR was associated with some undesirable cardiovascular effects in some of the participants. Systematic monitoring of cardiovascular parameters during treatment with venlafaxine-XR should be strongly recommended, especially in the elderly.

Age of Onset↗

Speed of improvement in sleep disturbance and anxiety compared with core mood symptoms during acute treatment of depression in old age.

OBJECTIVES: The objective of this study was to examine the relative speed of improvement in sleep disturbance and anxiety symptoms compared with core mood symptoms in acute treatment of late-life major depression. METHOD: The authors conducted secondary analysis of acute treatment data in 470 older patients treated in three federally funded studies. The authors compared rates of improvement in three Hamilton Rating Scale for Depression symptom clusters after stratification by study. RESULTS: Anxiety symptoms improved more slowly with antidepressant monotherapy and with combined pharmacotherapy/psychotherapy, whereas sleep symptoms improved at a similar rate as core mood symptoms. CONCLUSIONS: Anxiety symptoms tend to persist in patients with late-life depression.

Aged↗

Paroxetine treatment of primary insomnia in older adults.

OBJECTIVE: The goal of this study was to test the efficacy of paroxetine for primary insomnia in older adults. METHODS: Adults over age 55 with primary insomnia were randomly assigned to six weeks of double-blind treatment with paroxetine (N = 14) or placebo (N = 13). Outcome measures included persistence or resolution of insomnia; weekly diary measures of sleep quality, daytime alertness, and mood; and pre-/postpolysomnographic measures of sleep latency, wake time after sleep onset, and sleep efficiency. RESULTS: Although weekly diary-based measures showed improved subjective sleep quality, daytime alertness, and mood with paroxetine, the authors observed no effect on sleep efficiency or categorical response rates. CONCLUSION: Paroxetine appears to be ineffective for treating primary insomnia in old age.

Aged↗

Impact of prior treatment exposure on response to antidepressant treatment in late life.

OBJECTIVE: The objective of this study was to describe the correlates of prior antidepressant exposure and its association with response to protocolized treatment in older patients with major depression. METHODS: Based on their prior antidepressant treatment exposure, 193 elderly patients with a major depressive episode were divided into three groups: those with no prior treatment for their current episode (not treated [TN]), those with antidepressant trials of inadequate dose or duration ("treatment-inadequate" [TI]), and those with at least one adequate trial but persisting depression ("treatment-resistant" [TR]). All patients then received protocolized treatment with interpersonal psychotherapy (IPT) and paroxetine plus pharmacologic augmentation if needed. The demographic, clinical, and outcome information were compared among these three groups. RESULTS: Approximately one-third of the patients referred to the study had been adequately treated (TR), one-third had been inadequately treated (TI), and one-third were not treated for the current episode (TN). Treatment completion rates and reasons for dropping out did not differ statistically among TR, TI, and TN patients. TR patients took longer to respond (13.0 weeks) than either TI or TN patients (7.6 and 8.0 weeks, respectively). TR and TI patients had lower response rates (67% and 71%) than TN patients (86%). CONCLUSIONS: Prior treatment exposure is an important correlate of course and outcome in late-life depression. Most TR and TI patients eventually respond, but TR patients may require more intensive and longer courses of treatment than TI and TN patients.

Aged↗

Paroxetine: population pharmacokinetic analysis in late-life depression using sparse concentration sampling.

AIM: To develop a population pharmacokinetic (PK) model using sparse sampling of long-term treatment with paroxetine in elderly depressed subjects, incorporating CYP2D6 genotype as well as other covariates. METHODS: Elderly subjects (age>or=70 years) with nonpsychotic, nonbipolar major depressive disorder from the inpatient and outpatient clinic were treated with paroxetine in a 5-year clinical trial investigating 'Maintenance Therapies in Late-Life Depression' (MTLD-2). Plasma concentrations were collected during regular visits. CYP2D6 genotype was determined using polymerase chain reaction (PCR) for each individual. A nonlinear mixed-effects model was developed with NONMEM for these subjects who received 10-40 mg day-1 of paroxetine during treatment. One- and two-compartment models with linear and nonlinear elimination (Michaelis-Menten) were evaluated. PK parameters as well as interindividual and residual variability were estimated. The effects of age, weight, sex, race and CYP2D6 genotypes on the pharmacokinetics of paroxetine were evaluated. RESULTS: One hundred and seventy-one subjects with a mean age of 77 years (range 69-95) and a mean weight of 72.0 kg (range 32.9-137.0) were enrolled in the MTLD-2 clinical trial. A total of 1970 paroxetine concentrations were available for population PK analyses. Approximately 10 samples were taken per subject. A two-compartment nonlinear PK model with additive and proportional error provided the best base model for description of the data. Weight and CYP2D6 polymorphisms were found to have a significant effect on maximal velocity (Vm), whereas sex had an effect on volume of distribution of the central compartment. The Vm estimates in each of the CYP2D6 phenotypic groups were: 125 microg h-1 in poor metabolizer (n=1), 182 microg h-1 in intermediate metabolizers (n=28), 454 microg h-1 in extensive metabolizers (n=36) and 3670 microg h-1 in ultra-rapid metabolizers (n=5). CONCLUSIONS: The population PK model adequately described paroxetine data in this elderly depressed population. The data indicate that female and male subjects with different CYP2D6 polymorphisms have different elimination rates and therefore may need to be dosed differently based on metabolizer genotype.

Age Factors↗

Sleep in healthy seniors: a diary study of the relation between bedtime and the amount of sleep obtained.

The aim of this study was to determine whether naturally occurring inter-individual and intra-individual differences in bedtime selection in the elderly might be lawfully related to the amount of sleep that is obtained. A total of 128 seniors (63f, 65m) aged 70-92 years each provided a week of sleep diary data yielding a total of 896 subject-nights for analysis. From each subject-night the diary was used to derive measures of time in bed (TIB) and total sleep time (TST). These measures were used as dependent variables in mixed-effect linear models (nights nested within subjects) with the independent variable being bedtime for that subject-night, arbitrarily expressed as minutes since 19:00 hours. Although there were strong inter-individual and intra-individual differences, for both genders, bedtime had a statistically significant effect (P < 0.001) on both TIB and TST. We observed that later bedtimes were associated with less time in bed and less time asleep. On average between 7 and 8 min of less TIB and TST were associated with each 10-min delay in bedtime from 19:00 hours. These results are interpreted in terms of increases in sleep being derived from living in a better harmony with an earlier peaking circadian pacemaker characteristic of older age, although other possible mechanisms are also considered (e.g. age-dependent alterations in phase angle and homeostatic sleep need).

Aged↗

Ethical considerations in the conduct of electronic surveillance research.

The extant clinical literature indicates profound problems in the assessment, monitoring, and documentation of care in long-term care facilities. The lack of adequate resources to accommodate higher staff-to-resident ratios adds additional urgency to the goal of identifying more cost-effective mechanisms to provide care oversight. The ever expanding array of electronic monitoring technologies in the clinical research arena demands a conceptual and pragmatic framework for the resolution of ethical tensions inherent in the use of such innovative tools. CareMedia is a project that explores the utility of video, audio and sensor technologies as a continuous real-time assessment and outcomes measurement tool. In this paper, the authors describe the seminal ethical challenges encountered during the implementation phase of this project, namely privacy and confidentiality protection, and the strategies employed to resolve the ethical tensions by applying principles of the interest theory of rights.

Aged↗

Treating complicated grief: effects on sleep quality.

Complicated grief (CG) is characterized by recurrent distressing emotions and intrusive thoughts related to the loss of a loved one and avoidance of reminders of the deceased. Poor sleep quality characterizes CG. Cognitive-behavioral therapy and interpersonal psychotherapy reduce CG symptom severity. The effect of these treatments on sleep quality is not known, however. We investigated whether complicated grief treatments (CGTs) improve sleep quality, as assessed by the Pittsburgh Sleep Quality Index. Data collected from 95 adults who participated in a randomized controlled trial were reviewed. Poor sleep quality persisted despite clinically significant improvements in CG severity posttreatment. Given that sleep disturbance is a risk factor for poor health outcomes, adjunctive sleep interventions may be necessary to enhance CGT outcomes.

Adjustment Disorders↗

Indirect self-destructive behavior and overt suicidality in patients with complicated grief.

BACKGROUND: Complicated grief is associated with increased suicidal ideation in samples of bereaved individuals; however, suicidal behavior has not been assessed in these patients. Additionally, there are no reports of suicidality among help-seeking individuals with complicated grief. Therefore, we examined suicidal behavior and its correlates in 149 patients who signed informed consent statements to participate in a National Institute of Mental Health-funded treatment study of complicated grief. METHOD: All patients met criteria for complicated grief (Inventory of Complicated Grief score>or=25). Suicidality was assessed using a structured clinical interview administered prior to beginning treatment. Participants also completed self-report questionnaires and interview assessment measures rating the presence or absence of DSM-IV Axis I diagnosis and symptom severity. Data were gathered between April 2001 and April 2004. RESULTS: Thoughts of wanting to die following the death of a loved one were reported by 65% of participants. More than half of this group (38% of the study sample) engaged in self-destructive behavior, including 9% who made a suicide attempt and 29% who engaged in indirect suicidal behavior. In a multiple logistic regression model, only the severity of complicated grief symptoms (p<.0001) and history of a suicide attempt (p<.02) were significantly associated with postloss suicidal behavior. DISCUSSION: Consistent with reports of non-help-seeking bereaved people, a high rate of individuals seeking treatment for complicated grief endorsed a wish to die. Notably, 13% of this group made at least 1 suicide attempt, and 44% engaged in indirect self-destructive behavior. Given its frequency, this behavior should be included in assessment of bereaved people.

Attitude to Death↗

Outcomes of late-life anxiety disorders during 32 weeks of citalopram treatment.

BACKGROUND: Anxiety disorders are common in later life, but little is known about the long-term benefits and risks of pharmacotherapy. METHOD: 30 patients aged 60 years and older, with a DSM-IV anxiety disorder, entered a 32-week trial of citalopram. Data gathered at baseline and follow-up included anxiety symptoms using Hamilton Rating Scale for Anxiety (HAM-A) scores, quality of life using the Medical Outcomes Study 36-item Short Form (SF-36), and sleep using the Pittsburgh Sleep Quality Index (PSQI). Data analysis consisted of mixed-effect repeated measures models of HAM-A scores and pre-post comparison of SF-36 and PSQI scores. RESULTS: 30 persons entered treatment; most (27/30) had a primary DSM-IV diagnosis of generalized anxiety disorder (2 had panic disorder; 1 had posttraumatic stress disorder). Three subjects discontinued study medication due to side effects, 5 were terminated because of nonresponse, and 5 dropped out of the study for other reasons; thus, 17 subjects (57%) completed 32 weeks of treatment. Subjects' HAM-A scores improved significantly, with continuing improvements up until about 20 weeks of treatment. On the basis of a criterion of reduction in HAM-A to < 10 during the trial, 60% (18/30) of subjects were responders. Those who completed the 32-week trial had significant improvements in sleep and quality of life-including social functioning, vitality, mental health, and role difficulties due to emotional problems. CONCLUSIONS: In this 32-week study of citalopram for elderly persons with anxiety disorders, 60% responded. Those who received a full course of treatment experience significant improvements in quality of life and sleep quality.

Age Factors↗

The impact of psychosocial factors on late-life depression.

Mental illnesses in later life are multidimensional phenomena that occur in interpersonal, psychosocial, and biological contexts. With depression used as an example, the purpose of this article is to review how psychosocial variables contribute to the onset and maintenance of depression in late life, as well as influence treatment outcomes. Particular issues discussed are how these variables can be modified to prevent the onset and relapse of depression, how nonmodifiable risk factors can be addressed to prevent onset and relapse, and how research in this area needs to evolve to improve prevention and treatment.

Depressive Disorder↗

Prefrontal and striatal activation during sequence learning in geriatric depression.

BACKGROUND: Frontostriatal dysfunction is a primary hypothesis for the neurocognitive changes of depression in late life. The aim of the present study was to test this hypothesis with the use of functional magnetic resonance imaging (fMRI) tasks that are known to engage the prefrontal and neostriatal cognitive circuits. METHODS: Twenty-three elderly subjects (mean age, 69.9 years) participated: 11 subjects with a current major depressive episode and 12 nondepressed elderly control subjects. Subjects underwent fMRI while performing a concurrent implicit and explicit sequence learning task. Region of interest (ROI)-based analyses were conducted, focusing on the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, and the neostriatum. RESULTS: As expected, both the control and depressed subjects learned the sequence during both implicit and explicit conditions. During explicit learning, decreased prefrontal activation was found in the depressed subjects, along with increased striatal activation. The increased striatal activity in the depressed subjects was due to increased activity on the trials that violated the sequence. During implicit learning, no significant differences were found between the groups in the identified ROIs. CONCLUSIONS: The increased striatal activation on trials that violated the sequence demonstrates a greater response to negative feedback for depressed compared with control subjects. Our observations of significant differences in both prefrontal and striatal regions in the depressed elderly subjects relative to elderly control subjects supports the frontostriatal dysfunction hypothesis of late-life depression.

Aged↗

Treatment of complicated grief: a randomized controlled trial.

CONTEXT: Complicated grief is a debilitating disorder associated with important negative health consequences, but the results of existing treatments for it have been disappointing. OBJECTIVE: To compare the efficacy of a novel approach, complicated grief treatment, with a standard psychotherapy (interpersonal psychotherapy). DESIGN: Two-cell, prospective, randomized controlled clinical trial, stratified by manner of death of loved one and treatment site. SETTING: A university-based psychiatric research clinic as well as a satellite clinic in a low-income African American community between April 2001 and April 2004. PARTICIPANTS: A total of 83 women and 12 men aged 18 to 85 years recruited through professional referral, self-referral, and media announcements who met criteria for complicated grief. INTERVENTIONS: Participants were randomly assigned to receive interpersonal psychotherapy (n = 46) or complicated grief treatment (n = 49); both were administered in 16 sessions during an average interval of 19 weeks per participant. MAIN OUTCOME MEASURE: Treatment response, defined either as independent evaluator-rated Clinical Global Improvement score of 1 or 2 or as time to a 20-point or better improvement in the self-reported Inventory of Complicated Grief. RESULTS: Both treatments produced improvement in complicated grief symptoms. The response rate was greater for complicated grief treatment (51%) than for interpersonal psychotherapy (28%; P = .02) and time to response was faster for complicated grief treatment (P = .02). The number needed to treat was 4.3. CONCLUSION: Complicated grief treatment is an improved treatment over interpersonal psychotherapy, showing higher response rates and faster time to response.

Adaptation, Psychological↗

Prefrontal and striatal activation in elderly subjects during concurrent implicit and explicit sequence learning.

Decreased function in the prefrontal cortex (PFC) is regarded as a primary mechanism of cognitive aging. However, despite a strong association between the prefrontal cortex and the neostriatum, the role of the neostriatum in cognitive aging is less certain. In the current study, event-related functional MRI was used to distinguish the cognitive contributions of neostriatal and prefrontal function in elderly versus young subjects. Twenty healthy subjects, 9 elderly (mean age 67.6 years), and 11 young (mean age 22 years) performed a concurrent implicit and explicit sequence learning task while undergoing functional MR imaging. Both groups showed learning in both the implicit and explicit task conditions. Relative to the young subjects, the elderly subjects showed decreased activation in the left PFC during both implicit and explicit learning, decreased activation in the right putamen during implicit learning, and increased activation in the right PFC during explicit learning. Our results support the theory that changes in a network of brain regions, including the dorsolateral prefrontal cortex and the striatum, are related to cognitive aging. Moreover, these changes are observed during an implicit task, and thus do not seem to be mediated by awareness.

Adult↗

A randomized trial to improve the quality of treatment for panic and generalized anxiety disorders in primary care.

CONTEXT: Panic disorder and generalized anxiety disorder are prevalent in primary care, associated with poor functional outcomes, and are often unrecognized and ineffectively treated by primary care physicians. OBJECTIVE: To examine whether telephone-based collaborative care for panic and generalized anxiety disorders improves clinical and functional outcomes more than the usual care provided by primary care physicians. DESIGN: Randomized controlled trial. SETTING: Four Pittsburgh area primary care practices linked by a common electronic medical record system. Patients A total of 191 adults aged 18 to 64 years with panic and/or generalized anxiety disorder who were recruited from July 2000 to April 2002. Intervention Patients were randomly assigned to a telephone-based care management intervention (n = 116) or to notification alone of the anxiety disorder to patients and their physicians (usual care, n = 75). The intervention involved non-mental health professionals who provided patients with psychoeducation, assessed preferences for guideline-based care, monitored treatment responses, and informed physicians of their patients' care preferences and progress via an electronic medical record system under the direction of study investigators. MAIN OUTCOME MEASURES: Independent blinded assessments of anxiety and depressive symptoms, mental health-related quality of life, and employment status at baseline, 2-, 4-, 8-, and 12-month follow-up. RESULTS: At 12-month follow-up, intervention patients reported reduced anxiety (effect size [ES], 0.33-0.38; 95% confidence interval [CI], 0.04 to 0.67; P</=.02) and depressive symptoms (ES, 0.35; 95% CI, 0.25-0.46; P = .03); improved mental health-related quality of life (ES, 0.39; 95% CI, 0.10 to 0.68; P = .01); and larger improvements relative to baseline in hours worked per week (5.7; 95% CI, 0.1 to 11.3; P = .05) and fewer work days absent in the past month (-2.6; 95% CI, - 4.8 to -0.3; P = .03) than usual care patients. If working at baseline, more intervention patients than usual care patients remained working at 12-month follow-up (94% vs 79% [15% absolute difference, 0.7%-28.6%]; P = .04). CONCLUSIONS: Telephone-based collaborative care for panic disorder and generalized anxiety disorder is more effective than usual care at improving anxiety symptoms, health-related quality of life, and work-related outcomes.

Adult↗

Does education moderate neuropsychological impairment in late-life depression?

OBJECTIVE: The increased resistance of better-educated individuals to the cognitive effects of neuropathology has been conceptualized as reflecting brain reserve. This study examined whether educational level influences the degree of neuropsychological impairment associated with late-life depression. METHODS: The neuropsychological performances of 115 older depressed patients and of 44 comparison subjects of similar age and education were compared as a function of educational level. RESULTS: While depressed patients performed worse than comparison subjects on all the measures, the severity of this impairment (with respect to comparison subjects) did not differ with the educational level of the patients. CONCLUSIONS: Brain reserve, as indexed by the patients' level of education, does not mitigate the cognitive decrements associated with late-life depression.

Aged↗

Caregiving burden and psychiatric morbidity in spouses of persons with mild cognitive impairment.

BACKGROUND: While the deleterious psychosocial and mental health effects of dementia caregiving are firmly established, very little is known about the burdens or psychiatric outcomes of providing care to a spouse with less severe cognitive impairment, such as mild cognitive impairment (MCI). We characterized the nature and level of caregiver burden and psychiatric morbidity in spouses of persons diagnosed with MCI. METHODS: Interview assessments were completed on a cohort of 27 spouses of persons with a recent diagnosis of MCI. Patient medical records were reviewed to collect information regarding the MCI patient's medical history. RESULTS: Respondents endorsed elevated levels of both task-related responsibilities and subjective caregiver burden. Depression and anxiety symptom levels also showed some elevations. Measures of caregiver burden were significantly associated with depression and anxiety levels. In particular, even after controlling for demographic risk factors for distress, nursing task burden was correlated with elevated depressive symptoms, and greater lifestyle constraints were correlated with higher anxiety levels. CONCLUSIONS: Although caregiver burden and psychiatric morbidity levels were lower than those typically observed in family dementia caregiving samples, our findings suggest that MCI caregivers have already begun to experience distress in association with elevated caregiving burden. These individuals may be ideal targets for selective preventive interventions to maximize their psychological well-being as caregiving burdens related to their spouses' cognitive impairment increase.

Activities of Daily Living↗