Donepezil belongs to a class of drugs known as the 'acetylcholinesterase inhibitors' or AChEIs. These drugs help alleviate current symptoms and slow the development of new ones in people with Alzheimer's disease. Donepezil is one of four AChEIs currently approved by the FDA for such treatment.
Donepezil's Mechanism of Action
In the normal brain, a chemical called a neurotransmitter passes a signal from one brain cell, known as a neuron, to the next. One of the main causes of Alzheimer's disease is the loss of neurons containing the neurotransmitter acetylcholine, which is found in areas of the brain involved in learning and memory. Once a signal has been passed on by acetylcholine an enzyme called acetylcholinesterase, or AChE, breaks down the neurotransmitter to stop it working beyond when it is needed. As acetylcholine-containing neurons slowly decrease in people with Alzheimer's disease, there is less acetylcholine available for signaling. Therefore AChEIs such as donepezil prove necessary as they work by 'inhibiting' the actions of AChE and so increase the amount of acetylcholine available, even if fewer neurons produce it, says "Current Pharmaceutical Design".
Advantages of Donepezil
A number of studies have examined how donepezil can help people with Alzheimer's disease. One such includes the study by Bengt Winblad and colleagues and reported in the August 2001 edition of "Neurology." They found that after a year of treatment, ratings of intellectual impairment, physical function and emotional reaction improved significantly for those taking donepezil compared to those taking a placebo pill. They also found on a test of attention, memory and repetition that scores for those taking donepezil remained similar throughout the study, but those for people on the placebo pill steadily declined.
Others confirmed these findings, as detailed in a review carried out by Jacqueline Birks and Richard J Harvey, published in the "Cochrane Database of Systematic Reviews" in April 2006. They also discussed how donepezil produced benefits on scales of 'activities of daily living,' such as washing, dressing and eating, and of behavioral problems, such as agitation, aggression and delusions.
How these changes relate to a person's quality of life was shown in a study by David Geldmacher and colleagues in the July 2003 edition of the "Journal of the American Geriatrics Society." They found that people taking donepezil proved able to remain living in a community setting, such as their own home, before needing a nursing home placement for a significantly longer time than people not taking donepezil.
Disadvantages of Donepezil
Acetylcholine is not only a neurotransmitter in the brain, but also has actions in other parts of the body such as the digestive system. As such, a number of studies, including those detailed above, found that side effects of donepezil included nausea, diarrhea, vomiting and anorexia, with other side effects including insomnia, dizziness, fatigue, muscle cramps and rhinitis. However, Birks and Harvey report that these proved mostly moderate, and less problematic on a lower 5 mg, as opposed to a higher 10 mg, dose of donepezil and resolved after the first few weeks of treatment. However, for some they may not have tolerated enough to remain on treatment and they may have received another AChEI in its place.
References
- "Current Pharmaceutical Design;" Functional Neurochemistry of Alzheimer's Disease; Gsell et al; January 2004
- "Cochrane Database of Systematic Reviews;" Donepezil for Dementia Due To Alzheimer's Disease; Jacqueline Birks and Richard J Harvey; April 2006
- "Neurology;" A 1-year, Randomized, Placebo-Controlled Study of Donepezil in Patients With Mild to Moderate AD; Bengt Winblad; August 2001
- "Journal of the American Geriatrics Society;" Donepezil is Associated with Delayed Nursing Home Placement in Patients With Alzheimer's Disease; David Geldmacher; July 2003
- "International Journal of Clinical Practice;" Donepezil: Tolerability and Safety in Alzheimer's Disease; Raymond D Pratt; November 2002
