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Biomedical subjects

C F Reynolds

Publications and source records attributed to C F Reynolds.

At least 55 records · Page 3Linked to original sources
PubMed2000

Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression.

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

Adrenergic alpha-Agonists↗
PubMed2000

Decreased working memory and processing speed mediate cognitive impairment in geriatric depression.

BACKGROUND: While neuropsychological dysfunction is common in geriatric depression, not all aspects of cognition are equally affected. It has been suggested that depressed patients are impaired only in tasks that make heavy demands on processing resources and that a resource decrement therefore underlies the neuropsychological decrements seen in geriatric depression. The present study examined whether processing resources in the form of working memory and information processing speed are decreased in depression and whether a decrease in these resources actually mediates neuropsychological impairment. METHODS: Measures of processing resources were administered to elderly depressed patients prior to treatment and to age-matched controls. Patients whose depression remitted were retested as were the controls. Subjects also received neuropsychological tests of episodic memory and visuospatial performance. RESULTS: Depressed patients performed significantly worse on measures of both processing speed and working memory. While performance on these measures improved in patients whose depression remitted, the amount of improvement was no greater than that seen in the controls with repeat testing. Hierarchical regression analyses showed that depression explained a significant amount of variance on the neuropsychological tasks. However, if the variance associated with processing resources was removed first, depression no longer accounted for a significant amount of neuropsychological variance. CONCLUSIONS: Processing resources are decreased in elderly depressed patients and this decrease in resources appears to mediate impairments in several areas of neuropsychological functioning including episodic memory and visuospatial performance. The resource decrement persists after remission of the depression and thus may be a trait marker of geriatric depression.

Aged↗
PubMed2000

Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.

INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD. SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease. METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure. RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95% CI = 1.03, 1.76) in men and was 1.66 (95% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95% CI, 1.12- 1.98) and in women, was 2.21 (95% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men. CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.

Age Factors↗
PubMed2000

Changes in cognitive functioning following treatment of late-life depression.

OBJECTIVE: Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing, but little is known about the cognitive response to treatment for geriatric depression. The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression. METHOD: Subjects included 45 nondemented, elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects. All subjects were administered a battery of clinical measures, including cognitive screening instruments, before and after treatment. RESULTS: As a group, the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment. Among depressed patients with concomitant cognitive impairment at baseline, performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition. Despite the improvement following treatment, the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired, especially in the memory and initiation/perseveration domains. CONCLUSIONS: Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance, particularly in memory and executive functions. This subgroup of late-life depression patients is likely at high risk of developing progressive dementia.

Aged↗
PubMed2000

Comorbid anxiety disorders in depressed elderly patients.

OBJECTIVE: Anxiety disorders are common in adults with depressive disorders, but several studies have suggested a relatively low prevalence of anxiety disorders in older individuals with depression. This cross-sectional study measured current and lifetime rates and associated clinical features of anxiety disorders in depressed elderly patients. METHOD: History of anxiety disorders was assessed by using a structured diagnostic instrument in 182 depressed subjects aged 60 and older seen in primary care and psychiatric settings. Associations between comorbid anxiety disorders and baseline characteristics were measured. The modified structured instrument allowed detection of symptoms that met inclusion criteria for generalized anxiety disorder in a depressive episode. RESULTS: Thirty-five percent of older subjects with depressive disorders had at least one lifetime anxiety disorder diagnosis, and 23% had a current diagnosis. The most common current comorbid anxiety disorders were panic disorder (9.3%), specific phobias (8.8%), and social phobia (6.6%). Symptoms that met inclusion criteria for generalized anxiety disorder, measured separately, were present in 27.5% of depressed subjects. Presence of a comorbid anxiety disorder was associated with poorer social function and a higher level of somatic symptoms. Symptoms of generalized anxiety disorder were associated with a higher level of suicidality. CONCLUSIONS: Contrary to previous reports, the present study found a relatively high rate of current and lifetime anxiety disorders in elderly depressed individuals. Comorbid anxiety disorders and symptoms of generalized anxiety disorder were associated with a more severe presentation of depressive illness in elderly subjects.

Age Factors↗
PubMed2000

Fluvoxamine pharmacotherapy of anxiety disorders in later life: preliminary open-trial data.

The authors present data from an open trial of fluvoxamine (median daily dosage: 200 mg) in the treatment of generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder in 19 older outpatients (mean age = 66.8). Of the 12 subjects completing the 21-week trial, 8 achieved a good response (50% reduction in symptom measures) and 7 were rated as much or very much improved. Fluvoxamine pharmacotherapy also had a significant effect in reducing comorbid depressive symptoms and in increasing levels of functioning. These data support the effectiveness of fluvoxamine in older subjects with anxiety disorders (particularly generalized anxiety disorder) and warrant further double-blind, placebo-controlled evaluation.

Aged↗
PubMed2000

Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A prospective double-blind study in depressed elderly patients.

Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The authors examined the change from baseline EPS, measured by an objective rating scale, in a group of elderly depressed patients participating in an ongoing randomized, double-blind comparison of nortriptyline and paroxetine. Mild baseline EPS were present in both groups. After 6 weeks of antidepressant treatment, patients in the nortriptyline group showed a significant decrease in total EPS scores. Patients in the paroxetine group showed a similar decrease in EPS from baseline, which did not reach statistical significance. There was no significant difference between nortriptyline and paroxetine in the change in EPS.

Aged↗
PubMed2000

Treatment of men with major depression: a comparison of sequential cohorts treated with either cognitive-behavioral therapy or newer generation antidepressants.

OBJECTIVE: This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression. METHOD: Patients were enrolled in consecutive standardized 16-week treatment protocols conducted in the same research clinic. The first group (N = 52) was treated with Beck's model of CBT, whereas the second group (N = 23) received randomized but open-label treatment with either fluoxetine (N = 10) or bupropion (N = 13). Crossover to the alternate medication was permitted after 8 weeks of treatment for antidepressant nonresponders. The patient groups were well matched prior to treatment. Outcomes included remission and nonresponse rates, as well as both independent clinical evaluations and self-reported measures of depressive symptoms. RESULTS: Despite limited statistical power to detect differences between treatments, depressed men treated with pharmacotherapy had significantly greater improvements on 4 of 6 continuous dependent measures and a significantly lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring pharmacotherapy was late-emerging and partially explained by crossing over nonresponders to the alternate medication. The advantage of pharmacotherapy over CBT also tended to be larger among the subgroup of patients with chronic depression. CONCLUSION: Results of prior research comparing pharmacotherapy and CBT may have been influenced by the composition of study groups, particularly the gender composition, the choice of antidepressant comparators, or an interaction of these factors. Prospective studies utilizing flexible dosing of modern antidepressants and, if necessary, sequential trials of dissimilar medications are needed to confirm these findings.

Adult↗
PubMed1999

Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years.

CONTEXT: Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability. OBJECTIVE: To determine the efficacy of maintenance nortriptyline hydrochloride and interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years. DESIGN: A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist. SETTING: University-based psychiatric research clinic. PATIENTS: Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions. INTERVENTIONS: Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22). MAIN OUTCOME MEASURE: Recurrence of major depressive episode. RESULTS: The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval [CI], 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years. CONCLUSION: In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.

Adrenergic Uptake Inhibitors↗
PubMed1999

Consensus statement on the upcoming crisis in geriatric mental health: research agenda for the next 2 decades.

It is anticipated that the number of people older than 65 years with psychiatric disorders in the United States will increase from about 4 million in 1970 to15 million in 2030. The current health care system serves mentally ill older adults poorly and is unprepared to meet the upcoming crisis in geriatric mental health. We recommend the formulation of a 15- to 25-year plan for research on mental disorders in elderly persons. It should include studies of prevention, translation of findings from bench to bedside, large-scale intervention trials with meaningful outcome measures, and health services research. Innovative strategies are needed to formulate new conceptualizations of psychiatric disorders, especially those given scant attention in the past. New methods of clinical and research training involving specialists, primary care clinicians, and the lay public are warranted.

Age Distribution↗
PubMed1999

Residual analysis in random regressions using SAS and S-PLUS.

A program package RRAP: Random Regression Residual Analysis Program using SAS [1] and S-PLUS [2] is available for performing random regression residual analysis. The PROCEDURE MIXED from SAS is used for statistical inference. Both elementary-level and individual-level residuals are used. The S-PLUS programs provide: (1) a transformation to orthogonalize the elementary-level correlated residuals for standard regression residual analyses; and (2) several statistics and plots for checking model assumptions, assessing model fitting and detecting outlying individuals. RRRAP starts with a SAS Macro RRRAPMAC on the data followed by a S-PLUS Program DoRRRAP on a UNIX system.

Models, Statistical↗
PubMed1999

The art of clinical management in pharmacologic trials with depressed elderly patients: lessons from the Pittsburgh Study of Maintenance Therapies in Late-Life Depression.

The authors outline the clinical management methods used in a long-term study of depressed elderly patients and comment on the positive aspects of such interventions on the successful recruitment and retention of subjects. Psychosocial or clinical management (CM) is the "glue" that holds a successful drug trial together. CM is recognized to be an essential element for success in drug trials for geriatric depression. The authors also discuss potentially negative aspects of comprehensive CM, such as those obscuring a psychotherapeutic effect in comparative studies.

Aged↗