Medical uses of Donepezil
Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include gastrointestinal upset. It has an oral bioavailability of 100% and easily crosses the blood-brain barrier. Because it has a half-life of about 70 hours, it can be taken once a day.
Currently, there is no definitive proof that use of donepezil or other similar agents alters the course or progression of Alzheimer's disease. However, 6-12 month controlled studies have shown modest benefits in cognition and/or behavior. Pilot studies have reported that donepezil therapy may potentially have effects on markers of disease progression, such as hippocampal volume. Therefore, many neurologists, psychiatrists, and primary care physicians use donepezil in patients with Alzheimer's disease. 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 that there is no significant improvement in functional outcome, of quality of life, or of behavioral symptoms. However, NICE revised its guidelines to suggest that donepezil be used in moderate stage patients for whom the evidence is strongest. It is currently not licensed for use in the treatment of Alzheimer's disease in the UK at any other stage.
While the drug is currently indicated for mild to moderate Alzheimer's, there is also evidence from 2 clinical trials that indicates it may be effective for moderate to severe disease. An example of this is a Karolinska Institute paper published in The Lancet in early 2006, which states that donepezil improves cognitive function even in patients with severe Alzheimer's disease symptoms.
Donepezil (Aricept) should be used with caution in patient with; Cardiac Disease, Cardiac Conduction Disturbances, Chronic Obstructive Pulmonary Disease (COPD), Asthma, Severe Cardiac Arrhythmias and Sick Sinus Syndrome. Patient with gastrointestinal disorders should use caution because nausea/vomiting may occur. Nausea and vomiting 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.
Donepezil has been tested in other cognitive disorders (and is sometimes used off label) including Lewy body dementia and vascular dementia, but it is not currently approved for these indications. Donepezil has also been found to improve sleep apnea in Alzheimer's patients.
Donepezil has also been studied in patients with mild cognitive impairment, schizophrenia, attention deficit disorder, post-coronary bypass cognitive impairment, cognitive impairment associated with multiple sclerosis, CADASIL syndrome, and Down syndrome. A 3 year National Institutes of Health (NIH) trial in patients with mild cognitive impairment reported that donepezil was superior to placebo in delaying rate of progression to dementia during the initial 18 months of the study but this was not sustained at 36 months. In a secondary analysis, a subgroup of individuals with the apolipoprotein E4 genotype showed sustained benefits with donepezil throughout the study(Citation? Petersen 2005). However at this time donepezil is not indicated for prevention of dementia.
Recent studies suggest that donepezil can improve speech in children with autism. The studies found that speech of autistic children who were mild to moderately affected appeared to improve from the use of donepezil.
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