Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease. Caregiver preference for rivastigmine patches versus capsules for the treatment of Alzheimer disease. Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer's disease. A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial. Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer's dementia? A double-blind, placebo-controlled clinical trial.
Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease.
                To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia.
                We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation.
                This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD.
                Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.
                Copyright 2004 John Wiley & Sons, Ltd. Alzheimer disease (AD) has a significant impact on caregivers. Administering and managing medications is one of their many daily tasks. More effective modes of drug administration may benefit patient and caregiver, and may improve compliance. A prospective outcome of the IDEAL (Investigation of TransDermal Exelon in ALzheimer's disease) trial was to evaluate caregiver preference for rivastigmine patches compared with capsules. The 24-week, randomized, double-blind, double-dummy, placebo- and active-controlled IDEAL trial investigated once-daily rivastigmine patches vs twice-daily capsules in moderate AD patients. Caregivers rated patch adhesion throughout. The AD Caregiver Preference Questionnaire (ADCPQ) assessed patch vs capsule from caregivers' perspective, based on expectations, preferences, and satisfaction with treatment. A total of 1,059 caregivers completed the ADCPQ while their respective patients were on study drug. More than 70% of caregivers preferred the patch to capsules overall. The patch was preferred to capsules with respect to ease of use (p < 0.0001) and ease of following the schedule (p < 0.0001). Caregivers indicated greater satisfaction overall (p < 0.0001) and less interference with daily life (p < 0.01) with the patch vs capsules. The preference substudy of the IDEAL trial demonstrated that caregivers of AD patients preferred patches to capsules for drug delivery. Preference for the patch may indicate reduced caregiver stress, substantiated by greater satisfaction and less interference with daily life. These benefits may lead to improved compliance. To evaluate the efficacy and safety of rapidly titrated rivastigmine administered twice (BID) or three times (TID) daily in patients with mild to moderate Alzheimer's disease (AD).
                This was a 26 week international, randomised, double blind, placebo controlled study in which 678 patients with probable AD received placebo or rivastigmine 2-12 mg/day BID or TID. Primary outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog) and categorical analysis of the Clinician Interview Based Impression of Change incorporating caregiver information (CIBIC-Plus). Secondary outcomes were the CIBIC-Plus change from baseline, Progressive Deterioration Scale, ADAS-cogA, Mini-Mental State Examination and Global Deterioration Scale.
                At week 26, mean rivastigmine dose was 9.6 (2.76) mg/day in the TID group and 8.9 (2.93) mg/day in the BID group. Mean ADAS-cog changes from baseline in the TID and BID rivastigmine treated groups were -0.2 (SD 7.3) and 1.2 (SD 7.2) versus 2.8 (SD 7.2) for the placebo group (p<0.05). Differences between rivastigmine TID and placebo on the CIBIC-Plus categorical responder analysis were significant (31% vs 19%; p<0.05, intention to treat). No significant differences were seen between BID and placebo for this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal because of adverse events accounted for 17% of BID, 11% of TID and 9% of placebo patients.
                Rivastigmine administered as a BID or TID regimen significantly benefited cognitive, function and global performances in AD patients. The TID regimen showed a tendency for superior tolerability and permitted titration to higher doses, an outcome that is significant as the efficacy of rivastigmine is dose related. The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer's disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 +/- 1.0, 8.3 +/- 1.2, 8.9 +/- 1.3, and 10.7 +/- 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6-12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.
                Copyright 2005 S. Karger AG, Basel. To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance.
                Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial.
                Care facilities in the north east of England.
                93 patients with Alzheimer's disease, dementia, and clinically significant agitation.
                Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy).
                Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks.
                31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored > 10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points (95% confidence interval -25.3 to -4.0) lower (that is, worse) than in the placebo group at six weeks (P = 0.009) and -15.4 points (-27.0 to -3.8) lower at 26 weeks (P = 0.01). The corresponding changes with rivastigmine were -3.5 points (-13.1 to 6.2) lower at six weeks (P = 0.5) and -7.5 points (-21.0 to 6.0) lower at 26 weeks (P = 0.3).
                Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline. Recent studies suggest that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits, and other neuronal systems like monoaminergic hypofunction are involved. In several studies, selective serotonin reuptake inhibitors demonstrated promotion in neurogenesis in the hippocampus and enhanced memory and cognition. The aim of this study is to survey the effect of serotonin augmentation on cognition and activities of daily living in patients with Alzheimer's disease.
                The trial was designed as a 12-week randomized, placebo-controlled, double-blind study. One hundred twenty-two patients aged 55 to 85 years with mild-to-moderate Alzheimer's dementia were randomly allocated in 1 of the 3 treatment groups: fluoxetine plus rivastigmine, rivastigmine alone, or placebo group. Efficacy measures comprised assessments of cognition, activities of daily living, and global functioning. Hamilton Depression Scale also was used to assess changes in mood throughout the study.
                Fluoxetine plus rivastigmine and rivastigmine groups demonstrated improvement on measures of cognitive and memory without any significant difference; however, the former group did better in their activities of daily living and global functioning. Patients taking placebo had significant deterioration in all the efficacy measures. Patients taking rivastigmine or rivastigmine plus fluoxetine had improvements in Hamilton Depression Scale without significant differences.
                Concomitant use of selective serotonin-enhancing agents and acetyl cholinesterase inhibitors can provide greater benefit in activities of daily living and global functioning in patients with cognitive impairment. Because our study is preliminary, larger double-blind studies are needed to confirm the results.
Rivastigmine appears to be beneficial for people with mild to moderate Alzheimer's disease. In comparisons with placebo, improvements were seen in the rate of decline of cognitive function, activities of daily living, and severity of dementia with daily doses of 6 to 12 mg. Adverse events were consistent with the cholinergic actions of the drug. A transdermal patch has been tested in one trial, and there is evidence that the lower dose smaller patch is associated with fewer side effects than the capsules or the higher dose larger patch and has comparable efficacy to both. This review has not examined economic data.