Currently, no definitive proof shows the use of donepezil or other similar agents alters the course or progression of Alzheimer's disease (AD). However, 6 to 12-month controlled studies have shown modest benefits in cognition and/or behavior. In 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis of no significant improvement in functional outcome, quality of life, or behavioral symptoms. However, NICE revised its guidelines to suggest donepezil be used in moderate-stage patients for whom the evidence is strongest.
In clinical trials the most common adverse events leading to discontinuation were nausea, diarrhea, and vomiting.
Donepezil should be used with caution in people with cardiac disease, cardiac conduction disturbances, chronic obstructive pulmonary disease, asthma, severe cardiac arrhythmias and sick sinus syndrome.
Patients with gastrointestinal disorders should use caution because nausea or vomiting may occur. These symptoms may appear more frequent when initiating treatment or increasing the donepezil dose. Although occurrence of seizures is rare, patients who have a predisposition to seizures should be treated with caution.
Mechanism of action
The precise mechanism of action of donepezil in patients with Alzheimer's disease is not fully understood. Certainly Alzheimer's disease involves a substantial loss of the elements of the cholinergic system and it is generally accepted that the symptoms of Alzheimer’s disease are related to this cholinergic deficit, particularly in the cerebral cortex and other areas of the brain. It is note that the hippocampal formation play an important role in the processes of control of attention, memory and learning. Just the severity of the loss of cholinergic neurons of the central nervous system (CNS) has been found to correlate with the severity of cognitive impairment. Donepezil binds and inactivates reversibly the cholinesterases, thus inhibiting hydrolysis of acetylcholine. This results in an increased acetylcholine concentrations at cholinergic synapses.
A 2001 study suggested that donepezil can improve speech in autistic children. The study found the speech of autistic children that was originally mildly to moderately affected appeared to improve with the use of donepezil.
Research leading to the development of donepezil began in 1983 at Eisai, and in 1996, Eisai received approval from the United States Food and Drug Administration (USFDA) for donepezil under the brand Aricept, which it co-marketed with Pfizer. As of 2011, Aricept was the world's best-selling Alzheimer's disease treatment. The first generic donepezil became available in November 2010 with the USFDA approval of a formulation prepared by Ranbaxy Labs. In April 2011 a second generic formulation, from Wockhardt, received tentative USFDA marketing approval.
^Petersen, RC; Thomas, RG; Grundman, M; Bennett, D; Doody, R; Ferris, S; Galasko, D; Jin, S; Kaye, J; Levey, A; Pfeiffer, E; Sano, M; van Dyck, CH; Thal, LJ; Alzheimer's Disease Cooperative Study, Group (Jun 9, 2005). "Vitamin E and donepezil for the treatment of mild cognitive impairment.". The New England Journal of Medicine352 (23): 2379–88. doi:10.1056/nejmoa050151. PMID15829527.Cite uses deprecated parameters (help)