Rivastigmine transdermal patch and capsule in Alzheimer's disease: influence of disease stage on response to therapy.
ABSTRACT The cholinesterase inhibitor rivastigmine is approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). This exploratory, hypothesis-forming analysis assessed response to rivastigmine according to severity of dementia at baseline.
This was a retrospective analysis of a large randomized, placebo-controlled trial (ENA713D2320). AD patients treated with 9.5 mg/24 h rivastigmine patch, 17.4 mg/24 h rivastigmine patch, rivastigmine capsule (12 mg/day), or placebo were stratified according to baseline Mini-Mental State Examination (MMSE) scores: ≥7 to ≤12 (severe disease), ≥13 to ≤15 (moderately severe), ≥16 to ≤18 (moderate), or ≥19 to ≤25 (mild to moderate). Changes from baseline at Week 24 on Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) were assessed.
Based on baseline MMSE scores, 141, 228, 333, and 348 patients had severe, moderately severe, moderate, and mild to moderate dementia. Worsening of ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients receiving placebo were greater in patients with more severe dementia. Significant improvements versus placebo were seen with rivastigmine patch and/or capsule on ADAS-cog, ADCS-CGIC, and ADCS-ADL scores in patients with severe, moderately severe, and moderate AD (all p < 0.05). However, no significant improvements were seen in rivastigmine-treated patients with mild to moderate AD.
Rivastigmine benefits AD patients across dementia stages. Similar to previous cholinesterase inhibitor studies, greatest treatment effects with rivastigmine patch and capsule were seen in patients with more advanced dementia, most likely driven by greater placebo decline in this population.
SourceAvailable from: Wolfgang FroestlJournal of Alzheimer's disease: JAD 01/2013; 33(3):547-658. · 3.61 Impact Factor
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ABSTRACT: While there have been no new medications approved for the treatment of Alzheimer's disease (AD) or other dementias in Canada since 2004, the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) reviewed and updated the clinical practice guidelines on the pharmacological management of dementia that were published previously. This review focused on the literature for the pharmacological treatment of dementia based on studies published since the third CCCDTD in 2006. A literature search of English-language medical databases was preformed for studies pertaining to the pharmacological treatment of AD and other dementias that examined the management of cognitive and functional impairment, as well as neuropsychiatric symptoms. All previous recommendations were reviewed, and only those that required updating based on new published studies were revised. Several new recommendations were also added. Recommendations were rated for quality of evidence and were approved by consensus. There were 15 revised or new recommendations approved by consensus. The revised recommendations included acknowledging that cholinesterase inhibitors (ChEIs) possess a class effect and any of the agents can be used for AD across the spectrum of severity and with co-existing cerebrovascular disease. There was insufficient evidence to recommend for or against the use of ChEIs in combination with memantine for the primary indication of treating neuropsychiatric symptoms, or for the treatment of vascular dementia. Recommendations for the discontinuation of cognitive enhancers were revised and clarified, as well as the risks associated with discontinuing these drugs. ChEIs were recommended as a treatment option for dementia with Parkinson's disease. Risks associated with use of antipsychotics for neuropsychiatric symptoms were strengthened, and guidelines regarding the use of antidepressants for affective disturbances in dementia were weakened, and are now considered an option but not a firm recommendation. Valproate was recommended not to be used, and there was insufficient evidence to recommend for or against the use of selective serotonin reuptake inhibitors or trazodone for the treatment of agitation and aggression. In spite of the lack of new therapeutic agents for the treatment of dementia, recent studies have helped to clarify and strengthen recommendations to optimize the pharmacological management of these illnesses.Alzheimer's Research and Therapy 07/2013; 5(Suppl 1):S5. DOI:10.1186/alzrt201 · 3.50 Impact Factor
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ABSTRACT: The 24-week, prospective, randomized, double-blind ACTION study investigated the efficacy, safety, and tolerability of 13.3 versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD). Patients had probable AD and Mini-Mental State Examination scores ≥3-≤12. Primary outcome measures were as follows: Severe Impairment Battery (SIB) and AD Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV). Secondary outcomes were as follows: ADCS-Clinical Global Impression of Change (ADCS-CGIC), 12-item Neuropsychiatric Inventory (NPI-12), and safety/tolerability. Of 1014 patients screened, 716 were randomized to 13.3 mg/24 h (N = 356) or 4.6 mg/24 h (N = 360) patch. Baseline characteristics/demographics were comparable. Completion rates were as follows: 64.3% (N = 229) with 13.3 mg/24 h and 65.0% (N = 234) with 4.6 mg/24 h patch. The 13.3 mg/24 h patch was significantly superior to 4.6 mg/24 h patch on cognition (SIB) and function (ADCS-ADL-SIV) at Week 16 (P < 0.0001 and P = 0.049, respectively) and 24 (primary endpoint; P < 0.0001 and P = 0.025). Significant between-group differences (Week 24) were observed on the ADCS-CGIC (P = 0.0023), not NPI-12 (P = 0.1437). A similar proportion of the 13.3 mg/24 h and 4.6 mg/24 h patch groups reported adverse events (AEs; 74.6% and 73.3%, respectively) and serious AEs (14.9% and 13.6%). The 13.3 mg/24 h patch demonstrated superior efficacy to 4.6 mg/24 h patch on SIB and ADCS-ADL-SIV, without marked increase in AEs, suggesting higher-dose patch has a favorable benefit-to-risk profile in severe AD.CNS Neuroscience & Therapeutics 08/2013; DOI:10.1111/cns.12158 · 3.78 Impact Factor