A six‐month double‐blind, randomized, placebo‐controlled study of a transdermal patch in Alzheimer's disease–– rivastigmine patch versus capsule

Abstract

ObjectivesTo compare the efficacy, safety and tolerability of a novel rivastigmine transdermal patch with conventional rivastigmine capsules and placebo in patients with Alzheimer's disease (AD).MethodsIn this 24‐week, multicenter, double‐blind, double‐dummy, placebo‐ and active‐controlled trial, patients with probable AD were randomized to one of four treatment groups: 12 mg/day rivastigmine capsules; 10 cm2 (9.5 mg/24 h) rivastigmine patch; 20 cm2 (17.4 mg/24 h) rivastigmine patch; or placebo. Primary efficacy measures were the Alzheimer's Disease Assessment Scale—Cognitive subscale (ADAS‐Cog) and Alzheimer's Disease Cooperative Study––Clinical Global Impression of Change (ADCS‐CGIC).ResultsOne thousand one hundred and ninety five AD patients from 21 countries participated in the study. Treatment differences (vs placebo) on the ADAS‐Cog at Week 24 in 10 cm2 patch, 20 cm2 patch and capsule groups were 1.6 (p = 0.005), 2.6 (p < 0.001) and 1.6 (p = 0.003). Treatment differences on the ADCS‐CGIC were 0.3 (p = 0.01), 0.2 (p = 0.054) and 0.3 (p = 0.009). Comparison between the 10 cm2 patch and the capsule revealed non‐inferiority. Rates of nausea in the 10 cm2 patch and capsule groups were 7.2% and 23.1%, respectively; rates of vomiting were 6.2% and 17.0%, respectively. Moderate or severe skin irritation occurred in ≤10% patients across the four patch sizes (5, 10, 15 and 20 cm2).ConclusionsThe target dose of 10 cm2 rivastigmine patch provides efficacy similar to the highest doses of capsules with a superior tolerability profile. The transdermal patch with rivastigmine may offer convenience important to many caregivers and patients. Copyright © 2007 John Wiley & Sons, Ltd.

Evaluating High-Dose Rivastigmine Patch in Severe Alzheimer’s Disease: Analyses with Concomitant Memantine Usage as a Factor

“…Given that the efficacy of rivastigmine is dose-dependent and cholinergic deficits increase with disease severity [21,22], it seems clinically relevant to investigate the combination of memantine and high-dose rivastigmine in patients with severe AD. Studies with high-dose rivastigmine are made possible via transdermal delivery, which provides access to higher doses than can be reached with oral formulations, due to improved tolerability [23]. To our knowledge, these were the first analyses to investigate the concomitant use of 13.3 mg/24 h rivastigmine patch and memantine in a population with severe AD.…”

Medications used in dementia: a review of evidence

“…At lower doses (4 mg daily or lower), the differences were statistically significant for cognitive functions only (14). According to a 6-month, double-blind, placebo controlled RCT, Rivastigmine transdermal patch (9.5 mg/24 h) is as effective as the highest doses of oral formulations (15).…”

Treatment of apathy in Alzheimer's disease with transdermal rivastigmine: report of three cases

“…Although systematic reviews point to a lack of well-designed studies concerning this issue, anticholinesterasic drugs remain as an appropriate therapy for apathy. 3,4 The new presentation of transdermal rivastigmine has been studied as an option with fewer adverse effects (nausea and vomiting) when compared to other oral anticholinesterasic drugs, 5 but no studies concerning their use in behavioral symptoms have been conducted. In the cases reported above, there was a surprising improvement in the apathy of all patients, regardless of the changes in cognitive function.…”

“…Studies have reported that in patients taking lithium, the risk for developing abnormalities is approximately 11%; for presenting a cardiac abnormality it is close to 8%, and for Ebstein's anomaly it is approximately 2%. 4,5 Pregnant women with bipolar disorder have a 52% probability of experiencing recurrence of their illness during their pregnancy if lithium is discontinued. Additionally, a patient receiving lithium treatment will have a 37% likelihood of relapsing.…”