New York Consortium for Alzheimer Research and Education
The New York Consortium for Alzheimer Research and Education (N.Y.C.A.R.E.) is the joint effort of the Alzheimer’s Association New York City Chapter and the Education and Information Cores of the Alzheimer’s Centers — Columbia University, College of Physicians and Surgeons; Mount Sinai Medical Center; and New York University School of Medicine funded by the National Institute on Aging.

Research Update
News in AD Treatment: Aricept Generic and Aricept 23 mg

Generic Aricept (Donepezil): Is it the same as Aricept?
Patients without prescription coverage, and those whose insurance companies are asking them to change to the generic, are asking the question: Is there anything bad about switching to generic donepezil. Generic donepezil is available as 5 and 10 mg in both regular and orally disintegrating tablets. The 23 mg dose is only available as Aricept. The generic versions currently available have an “AB” rating by the FDA, which means that they are considered equivalent to the brand-name drug. The only difference between them and Aricept may be in the inert ingredients (fillers, dyes, etc.) to which a small minority of patients may be sensitive. Bottom line: there is no reason not to try the generic form of Aricept.

Aricept 23
In July of 2010, the US FDA approved a 23 mg once-daily tablet of Aricept (donepezil). Many patients and families have asked whether it is appropriate for them to try it. To answer that question we have to examine the research.

An initial pilot study of doses of Aricept up to 20mg, in a small trial of 31 patients was published by Doody et al, in Drugs in Aging in 2008 showed the safety (?) and feasibility of using these doses in patients. The approval of Aricept 23 mg was based on a double-blind, randomized study, evaluating Aricept 23 mg vs. Aricept 10 mg in 1467 patients with moderate to severe Alzheimer’s disease over the course of 6 months. What they found was that the group taking the 23 mg tablet had a small, but significant benefit on a measure called the Severe Impairment Battery (SIB), compared to those taking 10 mg. The SIB measures performance on simple cognitive tasks such as following directions, simple tests of language and memory, and recognizing objects. Scores on the SIB can range from 0-100. The difference in the change in scores between the 10mg group and the 23 mg group was 2.2 points (P = .0001) over the 6 month study period. The other measure used in the study was the “Clinician’s Interview-Based Impression of Change Plus Caregiver Input” (CIBIC plus), which measures global function. While there was no statistically significant difference between the groups as a whole on this measure, when the researchers divided the patients into two groups based on severity of impairment (MMSE 0-16 vs. 17-20), they found a greater treatment effect (about 3 points on the SIB), as well as a statistically significant benefit in the CIBIC plus in the more impaired group (Fellows et al., 2010). It is important to note that the frequency of side effects was greater with the Aricept 23 mg dose,, including more cases of nausea (11.8% vs. 3.4%), vomiting (9.2% vs. 2.5 %), diarrhea (8.3% vs. 5.3%) and loss of appetite (5.3% vs. 1.7%).

The question remains: Who should try the higher dose of Aricept?
The FDA has approved Aricept 23 mg only for patients with moderate to severe AD. This is consistent with the research data that showed greatest benefit in the patients with MMSE <16. There is currently no evidence that this dose is more helpful in earlier stage disease than the lower 10 mg. dose of Aricept (donepezil). Although the combination of Aricept 23 mg and memantine (Namenda) has not been studied, there is no reason to think that there would be any new concerns about using these two medications together.

Therefore, in patients with moderate to severe disease, who are already stable on donepezil (Aricept) 10 mg, it may be worth a trial of higher dose Aricept. In those for whom lack of insurance or prohibitive co-pays preclude using Aricept 23 mg, a trial of higher dose (e.g., 15 mg and then increasing to 20 mg) of generic donepezil, could be tried. The increased incidence of gastrointestinal side effects requires careful observation of patients.

In general, studies of the cholinesterase inhibitors (Aricept, Razadyne, Exelon) were conducted with patients in the mild to moderate stages of Alzheimer’s disease, These studies have all demonstrated the efficacy of these medications when givien in adequate doses (e.g., 16-32 mg daily of Razadyne (galantamine), 6-12 mg daily of Exelon (rivastigmine), 5-10 mg of Aricept (donepezil). In an initial study of the Exelon Patch, there was no additional benefit from a higher dose To date there have been no published results of trials of higher doses of the other cholinesterase inhibitors (Razadyne (galantamine) or Exelon (rivastigmine) in more impaired patients, or in those who have been stable on the currently approved maximal dose. There is currently an ongoing trial of a higher dose Exelon patch in severe AD (MMSE 3-12).

The current state of pharmacologic treatment is modest at best. Many research facilities around the world, including the three ADC’s in New York City are working tirelessly to develop new and improved treatments that will be disease-modifying compounds. Many studies are focusing on those with mild or no symptoms who may have risk factors for the disease. It is hoped that this early treatment will maximize the quality of life for those who may be affected and their families.

1. Farlow MR, Salloway S, Tariot PN, et al. Effectiveness and tolerability of highdose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer’s disease: A 24-week, randomized, double-blind study. ClinTher. 2010 Jul;32(7):1234-51.

2. Doody RS, Corey-Bloom J, Zhang R, et al. Safety and Tolerability of Donepezil at Doses up to 20 mg/day. Results from a Pilot Study in Patients with Alzheimer’s Disease. Drugs Aging. 2008;25(2):163-74.