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Thomas McRae

Publications and source records attributed to Thomas McRae.

7 recordsLinked to original sources
PubMed2006

Patterns of cholinesterase-inhibitor use in the nursing home setting: a retrospective analysis.

OBJECTIVE: This study compared dosing and utilization patterns of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine, and galantamine in the nursing home setting. METHODS: An exploratory, retrospective analysis of prescription claims data from January 1, 2001, to March 31, 2003, was conducted using data from a nationwide network of long-term care facilities in the United States. Nursing home residents with > or =1 new prescription for donepezil, rivastigmine, or galantamine during the index period from June 1, 2001, through March 31, 2002, were identified, and those who received an index prescription for a ChEI >45 days after nursing home admission and remained in the nursing home for > or=1 year after the initiation of ChEI treatment were included in the analysis. Utilization patterns were evaluated based on prescription claims for 1 year after the initiation of therapy. The study end points were the proportions of patients discontinuing or switching ChEI therapy, the proportion reaching an effective daily dose of ChEI therapy, the mean time to effective dose, and the mean daily dosage. RESULTS: : Two thousand eight hundred seventy-three residents of 1417 nursing homes were included in this analysis, of whom 1906 (66.3%) were prescribed donepezil, 507 (17.6%) rivastigmine, and 460 (16.0%) galantamine. The proportion of residents who were prescribed an effective dose at any point during the 1-year study period was significantly greater for donepezil than for rivastigmine or galantamine (99.3%, 72.5%, and 65.1%, respectively; both, P < 0.001). The difference between rivastigmine and galantamine also was statistically significant (P < 0.014). Donepeziltreated residents had a significantly shorter mean time to effective dose than rivastigmine- and galantamine-treated residents (1.5, 76.7, and 99.9 days; P < 0.001). The mean daily dosage of donepezil was above the effective dose throughout the study period, whereas the mean daily dosage was below the effective dose for the first 3 months with rivastigmine and did not approach the effective dose for galantamine until month 12. ChEl therapy was discontinued during the study period by 43.1%, 46.2%, and 47.0% of donepezil-, rivastigmine-, and galantamine-treated residents, respectively. The corresponding proportions of residents switching therapy were 3.3%, 4.7%, and 2.0%. CONCLUSIONS: The results of this study suggest that early effective dosing occurred more often with donepezil than with rivastigmine or galantamine in these nursing home residents. Almost half of residents discontinued donepezil, rivastigmine, or galantamine, whereas rates of switching from one ChEI to another were low.

Adult↗
PubMed2006

Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders.

OBJECTIVE: The objective of this study was to conduct exploratory analyses of data pertaining to the efficacy of donepezil treatment of patients with severe behavioral disturbances. Preliminary studies suggest that cholinesterase inhibitors, including donepezil, may reduce behavioral disturbances in patients with Alzheimer disease (AD). Most patients included in clinical trials have had low levels of psychopathology at baseline, and the effect of cholinesterase inhibitors on patients with more severe behavioral disturbances is unknown. The authors report the effects of donepezil on behavioral disturbances in patients with relatively severe psychopathology at baseline. METHODS: This is a hypothesis-driven secondary analysis of a three-phase study involving donepezil and sertraline. In phase 1, psychotropic agents were withdrawn; in phase 2, patients were treated in an open-label fashion with donepezil for 8 weeks; and in phase 3, patients on donepezil were randomized to receive placebo or sertraline for an additional 12 weeks. The data set analyzed is comprised of the patient population treated with donepezil (without sertraline) for 20 weeks. One hundred twenty patients were included in the analyses. Mean age was 76 years, average Mini-Mental State Examination Score was 18, and mean Neuropsychiatric Inventory (NPI) total score was 30. Primary efficacy assessments were the NPI, the Clinical Global Impression-Improvement, and the Clinical Global Impression-Severity scales. Secondary measures included the Behavioral Pathology in Alzheimer's Disease Rating Scale, The Hamilton Depression Rating Scale, and the Alzheimer's Disease Functional Assessment and Change Scale. RESULTS: Excellent concurrent validity was noted between the NPI and the Behavioral Pathology in Alzheimer's Disease Rating Scale. The total score of the NPI was significantly reduced over the 20 weeks of therapy with donepezil. Sixty-two percent of patients had at least a 30% reduction in the total NPI score (significantly greater than the number with no meaningful response). Likewise, more patients had total or partial resolution of depression and delusions than those who had no meaningful change. Factor analysis of baseline NPI data revealed five factors, including a psychosis factor, an agitation factor, mood factor, frontal lobe function factor, and appetite and eating disorders factor. Clinically meaningful treatment effect sizes were notable for the delusion factor (0.340) and the mood factor (0.39). There were significant correlations between the Clinical Global Impression-Improvement and reductions in mood and agitation scores. CONCLUSION: The results of these analyses suggest that donepezil reduces behavioral symptoms, particularly mood disturbances and delusions, in patients with AD with relatively severe psychopathology.

Aged↗
PubMed2004

A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer's disease in outpatients treated with donepezil.

OBJECTIVE: To examine the safety and efficacy of sertraline augmentation therapy in the treatment of behavioral manifestations of Alzheimer's disease (AD) in outpatients treated with donepezil. METHODS AND MATERIALS: Patients with probable or possible AD, and a Neuropsychiatric Inventory (NPI) total score >5 (with a severity score > or =2 in at least one domain), were treated with donepezil (5-10 mg) for 8 weeks, then randomly assigned to 12 weeks of double-blind augmentation therapy with either sertraline (50-200 mg) or placebo. Primary efficacy measures were the 12-item Neuropsychiatric Inventory (NPI) and the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales. RESULTS: 24 patients were treated with donepezil+sertraline and 120 patients with donepezil+placebo. There were no statistically significant differences at endpoint on any of the three primary efficacy measures. However, a linear mixed model analysis found modest but statistically significantly greater improvements in the CGI-I score on donepezil+sertraline. Moreover, in a sub-group of patients with moderate-to-severe behavioral and psychological symptoms of dementia, 60% of patients on sertraline vs 40% on placebo (p = 0.006) achieved a response (defined as > or = 50% reduction in a four-item NPI-behavioral subscale). One adverse event (diarrhea) was significantly (p < 0.05) more common in the donepezil+sertraline group compared to the donepezil+placebo group. CONCLUSION: Sertraline augmentation was well-tolerated in this sample of AD outpatients. In addition, post hoc analyses demonstrated a modest but statistically significant advantage of sertraline over placebo augmentation in mixed model analyses and a clinically and statistically significant advantage in a subgroup of patients with moderate-to-severe behavioral and psychological symptoms of dementia.

Aged↗
PubMed2004

Impact of donepezil treatment for Alzheimer's disease on caregiver time.

OBJECTIVE: To assess the impact of donepezil treatment compared with placebo on caregiver time spent assisting patients with Alzheimer's disease (AD). RESEARCH DESIGN AND METHODS: Patient and caregiver data were collected as part of a 1-year, prospective, double-blind, randomized, placebo-controlled trial. The Resource Utilization in Dementia (RUD) questionnaire was used to record caregiver time at study baseline and at Weeks 12, 24, 36, and 52. This analysis focuses solely on those caregivers who were actively (> 0 h/day reported on the RUD) providing care at study baseline. MAIN OUTCOME MEASURES: The change in time relative to baseline that caregivers spent assisting patients over the course of the study. RESULTS: The active caregiver population was composed of 96 caregivers of donepezil-treated patients and 94 caregivers of patients receiving placebo. Over the course of the 1-year study, and as the condition of the AD patients deteriorated, it was expected that caregiver time would increase. As expected, after 52 weeks, caregivers of placebo patients were providing almost 2 h each day (106.8 min) more care than they had done at study baseline. For those caregivers of donepezil-treated patients, although they were spending more time caring than they had done at study baseline, their time burden had only increased by 42.6 min more each day. This difference in caring time between the 2 groups, relative to baseline at Week 52, was 1.1 h (64.2 min) each day, and was significant (p = 0.03). CONCLUSION: Caregiver time devoted to helping an AD patient typically increases with the severity of the disease. By helping the patient maintain his/her ability to perform activities of daily living for longer, treatment with donepezil is not only beneficial to the patient, but also has positive time-burden implications for the caregiver.

Activities of Daily Living↗
PubMed2003

Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease.

OBJECTIVES: To assess the relationship between donepezil treatment and time to nursing home placement (NHP) for patients with Alzheimer's disease (AD). DESIGN: Observational follow-up of patient NHP and vital status. SETTING: Community. PARTICIPANTS: Patients previously enrolled in one of three randomized, double-blind, placebo-controlled clinical trials of donepezil and two subsequent open-label studies (total N = 1,115); 671 patients provided complete data for analysis. MEASUREMENTS: Data were obtained through follow-up interviews with caregivers and chart reviews of patients with AD. Comparison groups were defined by whether patients received an effective dose of donepezil (>/=5 mg/d; >/=80% compliance) for specific numbers of weeks during the double-blind or open-label trial phase, in both phases, or in neither. Cox proportional hazards models were used to estimate risk ratios for NHP and survival curves from which median times to NHP were estimated for first dementia-related placement of longer than 2 weeks and permanent placement. The models were adjusted for age, sex, baseline Mini-Mental State Examination score, whether the caregiver was a spouse, caregiver continuity, and use of other cholinesterase inhibitors after the clinical trials. RESULTS: Use of donepezil of 5 mg/d or more was associated with significant delays in NHP. A cumulative dose-response relationship was observed between longer-term sustained donepezil use and delay of NHP. When donepezil was taken at an effective dose for at least 9 to 12 months, conservative estimates of the time gained before NHP were 21.4 months for first dementia-related NHP and 17.5 months for permanent NHP. CONCLUSION: Use of donepezil by AD patients resulted in significant delays in NHP. Long-term use of donepezil may help AD patients live longer in community settings, with consequent personal, social, and economic benefits.

Aged↗
PubMed2003

A large, community-based, open-label trial of donepezil in the treatment of Alzheimer's disease.

This phase III trial was conducted to evaluate the safety and efficacy of donepezil in Alzheimer's disease (AD) patients with a greater range of comorbid conditions and concomitant medication use than those previously evaluated in placebo-controlled studies. Patients (n = 1,035) with mild to moderate probable or possible AD were enrolled from 255 sites in the USA; 894 (86%) completed the trial. Mean age was 74.9 years (+/- 7.8); baseline standardized Mini-Mental State Examination (sMMSE) score was 19.77 (+/- 5.4). Nearly all patients had at least 1 prior or comorbid medical condition (97%) or were taking at least 1 concomitant medication (93%). Safety assessments included recording treatment-emergent adverse events (AEs). To confirm comparability with past studies, efficacy was measured using the sMMSE. Over the 12-week study period, the mean sMMSE score increased by 1.54 points over baseline (p < 0.0001) in donepezil-treated patients. Most AEs (64%) were mild, and the occurrence of cholinergic-induced AEs was significantly lower after a dose increase at 4 weeks than that seen with a dose increase after 1 week in previous trials. Risk ratios for gastrointestinal side effects were not significantly increased by the use of aspirin or nonsteroidal anti-inflammatory drugs. Risk ratios for bradycardia were not significantly increased by the use of beta-blockers, nondihydropyridine calcium channel blockers or digoxin. Therefore, donepezil improved cognition, as measured by the sMMSE, and was well tolerated despite high concomitant medication use and extensive comorbidity. These results highlight donepezil as a safe and effective treatment for AD patients typically seen by community-based physicians.

Adult↗