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Management of Mild to Moderate Alzheimer Disease

Defining the Role of Rivastigmine

  • Drugs In Disease Management
  • Published:
Disease Management & Health Outcomes

Abstract

Alzheimer disease is a common, progressive neurodegenerative disorder of the elderly, affecting approximately 3% of individuals 65–74 years of age, and up to half of those aged ≥85 years. Along with progressive loss of memory and cognitive function, other symptoms include depression and behavioral and motor disturbances. Some estimates of the cost of Alzheimer disease in the US exceed $US100 billion annually.

While no drug clearly slows progression of Alzheimer disease, cholinesterase inhibitors have provided the greatest symptomatic benefit, particularly in improving or delaying the decline in cognitive function. As such, rivastigmine, donepezil, and galantamine are recommended as first-line treatment options for patients with mild to moderate Alzheimer disease.

Rivastigmine has been evaluated in a number of clinical trials, including two large multicenter studies in patients with mild to moderate Alzheimer disease. In the observed-case analyses of these 26-week pivotal trials, rivastigmine 3–6mg twice daily was consistently associated with statistically significant benefits versus placebo in key measures of cognition, global function, and activities of daily living. Intent-to-treat analyses showed similar results, with most differences versus placebo achieving statistical significance. Follow-up data of up to 5 years’ total duration demonstrated long-term cognitive benefits with continued rivastigmine therapy.

As with all cholinesterase inhibitors, gastrointestinal adverse effects including nausea, vomiting, diarrhea, and anorexia are relatively common with rivastigmine. Individualized dosage titration and administration with food are recommended to minimize these problems, which are generally of mild to moderate severity and limited duration.

Pharmacoeconomic analyses of rivastigmine in mild to moderate Alzheimer disease indicate that the cost of the drug is essentially off-set by reductions in other costs after about 2 years of therapy, primarily by delaying institutionalization. Most were modeled analyses from the US, Canada, and the UK conducted from societal or provider perspectives.

In conclusion, rivastigmine is one of a very limited number of first-line medications for the symptomatic treatment of mild to moderate dementia in Alzheimer disease. Along with improving or delaying the decline in cognitive function, rivastigmine also has beneficial effects on global function, activities of daily living, and behavioral problems. Rivastigmine is also a useful treatment option for patients not responding to therapy with other cholinesterase inhibitors. Potential advantages of rivastigmine include its low drug interaction potential and dual inhibitory effect on both acetyl- and butyrylcholinesterase. Large, randomized comparisons between rivastigmine, donepezil, and galantamine are needed to provide further insight into clinically significant differences between these cholinesterase inhibitors.

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    Greg L. Plosker & Gillian M. Keating

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Plosker, G.L., Keating, G.M. Management of Mild to Moderate Alzheimer Disease. Dis-Manage-Health-Outcomes 12, 55–72 (2004). https://doi.org/10.2165/00115677-200412010-00005

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