Donepezil
Donepezil
Definition
Donepezil is a drug used to treat mild to moderate dementia. In the United States, donepezil is sold under the trade name Aricept.
Purpose
Donepezil is used to help treat symptoms in individuals with mild to moderate Alzheimer’s disease. The drug may cause small improvements in dementia for a short period of time, but donepezil does not stop the progression of Alzheimer’s disease.
Description
The U.S. Food and Drug Administration (FDA) has approved donepezil for treatment of the symptoms of Alzheimer’s disease. In Alzheimer’s disease, some cells in specific regions of the brain die. Because of this cell death, these brain cells lose their ability to transmit nerve impulses. Brain cells normally transmit nerve impulses by secreting various chemicals known as neurotransmitters.
Brain cells that make and secrete a neurotransmitter called acetylcholine are affected early in the course of Alzheimer’s disease. Donepezil helps prevent the breakdown of acetylcholine in the brain, thus temporarily increasing its concentration. In doing so, donepezil may improve the thinking process by facilitating nerve impulse transmission within the brain.
Donepezil is available as tablets in two different strengths. It is broken down by the liver.
Recommended dosage
The initial dosage of donepezil is 5 mg taken at bedtime. This dose should be continued for four to six weeks. The dosage may then be increased to 10 mg at bedtime, but there is no clear evidence that the higher dosage is more beneficial. However, the higher dosage is likely to cause more side effects.
Precautions
Donepezil may slow heart rate, increase acid in the stomach, make urination difficult, cause breathing difficulties, and may make it more likely for people to have seizures. Therefore, people with certain heart conditions, those who are prone to stomach ulcers, people with bladder obstruction, individuals with asthma or chronic obstructive pulmonary disease, and people with a history of seizure disorders should use donepezil carefully under close physician supervision.
KEY TERMS
Acetylcholine —A naturally occurring chemical in the body that transmits nerve impulses from cell to cell. Generally, it has opposite effects from dopamine and norepinephrine; it causes blood vessels to dilate, lowers blood pressure, and slows the heartbeat. Central nervous system well-being is dependent on a balance among acetylcholine, dopamine, serotonin, and norepinephrine.
Dementia —A group of symptoms (syndrome) associated with a progressive loss of memory and other intellectual functions that is serious enough to interfere with a person’s ability to perform the tasks of daily life. Dementia impairs memory, alters personality, leads to deterioration in personal grooming, impairs reasoning ability, and causes disorientation.
Milligram (mg) —One-thousandth of a gram. A gram is the metric measure that equals about 0.035 ounces.
Neurotransmitter —A chemical in the brain that transmits messages between neurons, or nerve cells.
People taking donepezil should be reassessed periodically to determine whether the drug is providing any benefits. When caregivers feel the drug is no longer beneficial, it may be stopped.
Side effects
More than 5% of people taking donepezil experience difficulty sleeping, dizziness, nausea, diarrhea, muscle cramps, headache, or other pains.
Diarrhea, nausea, and vomiting occur more often with the 10-mg dose than the 5-mg dosage. These adverse effects are usually mild, short-lived, and typically subside when the drug is stopped. Other less common side effects are abnormal dreams, depression , drowsiness, fainting, loss of appetite, weight loss, frequent urination, arthritis, and easy bruising.
Interactions
Recent research has found that the effects of donepezil on Alzheimer’s disease may be enhanced through combination therapy with memantine (Namenda). According to a study in the Journal of the American Medical Association in 2004, studies have shown that the use of memantine in combination therapy with donepezil is frequently more effective than the use of donepezil alone in the treatment of moderate to severe Alzheimer’s disease. Using memantine and donepezil in combination therapy does not affect the pharmacokinetics of either drug. Clinical trials have shown such combination therapy to be both safe and effective, although the safety precautions for both drugs must be considered before combination therapy is undertaken.
Many drugs may alter the effects of donepezil; likewise, donepezil may alter the action of other drugs. Drugs such as dicyclomine, phenytoin, carbamazepine , dexamethasone, rifampin, or phenobarbital may lessen the effects of donepezil. Other drugs such as bethanechol, ketoconazole, or quinidine may increase some of the side effects associated with donepezil. When donepezil and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil) or naproxen (Aleve) are used together, there may be an increased tendency to develop stomach ulcers. Donepezil may increase the side effects associated with use of fluvoxamine , an antidepressant. If succinylcholine, a drug commonly used during anesthesia, is used with donepezil, prolonged muscle paralysis may result.
Resources
BOOKS
Facts and Comparisons Staff. Drug Facts and Comparisons. 6th ed. St. Louis: Facts and Comparisons, 2002.
Mosby Staff. Mosby’s Medical Drug Reference. St. Louis, MO: Mosby, 1999.
VandenBos, Gary R., ed. APA Dictionary of Psychology. Washington, D.C.: American Psychological Association, 2007.
PERIODICALS
Asp, Elissa, and others. “Verbal Repetition in Patients with Alzheimer’s Disease Who Receive Donepezil.” International Journal of Geriatric Psychiatry 21.5 (May 2006): 426–31.
Chen, Xiying, and others. “Donepezil Effects on Cerebral Blood Flow in Older Adults with Mild Cognitive Deficits.” Journal of Neuropsychiatry & Clinical Neurosciences 18.2 (Sept. 2006): 178–85.
Cholongitas, Evangelos, Chrysoula Pipili, and Maria Dasenaki. “Recurrence of Upper Gastrointestinal Bleeding After Donepezil Administration.” Alzheimer Disease and Associated Disorders 20.4 (Oct.-Dec. 2006): 326.
Cummings, Jeffrey L., Thomas McRae, and Richard Zhang. “Effects of Donepezil on Neuropsychiatric Symptoms in Patients with Dementia and Severe Behavioral Disorders.” American Journal of Geriatric Psychiatry 14.7 (July 2006): 605–12.
Feldman, Howard H., Frederick A. Schmitt, and Jason T. Olin. “Activities of Daily Living in Moderate-to-Severe Alzheimer Disease: An Analysis of the Treatment Effects of Memantine in Patients Receiving Stable Donepezil Treatment.” Alzheimer Disease and Associated Disorders 20.4 (Oct.-Dec. 2006): 263–68.
Hogan, David B. “Donepezil for Severe Alzheimer’s Disease.” Lancet 367.9516 (Apr. 2006): 1031–32.
Kitabayashi, Yurinosuke, and others. “Donepezil-Induced Nightmares in Mild Cognitive Impairment.” Psychiatry and Clinical Neurosciences 60.1 (Feb. 2006): 123–24.
Maruyama, Masahiro, and others. “Benefits of Combining Donepezil Plus Traditional Japanese Herbal Medicine on Cognition and Brain Perfusion in Alzheimer’s Disease: A 12-Week Observer-Blind, Donepezil Mono-therapy Controlled Trial.” Journal of the American Geriatrics Society 54.5 (May 2006): 867–71.
Mazeh, D., and others. “Donepezil for Negative Signs in Elderly Patients with Schizophrenia: An Add-On, Double-Blind, Crossover, Placebo-Controlled Study.” International Psychogeriatrics 18.3 (Sept. 2006): 429–36.
Ringman, John M., and Jeffrey L. Cummings. “Current and Emerging Pharmacological Treatment Options For Dementia.” Behavioural Neurology 17.1 (2006): 5–16.
Schredl, M., and others. “The Effect of Donepezil on Sleep in Elderly, Healthy Persons: A Double-Blind Placebo-Controlled Study.” Pharmacopsychiatry 39.6 (Nov. 2006): 205–208.
Stiles, Melissa M., and Sandra Martin. “Does Treatment with Donepezil Improve Memory for Patients With Mild Cognitive Impairment?” Journal of Family Practice 55.5 (May 2006): 435–36.
Tariot, Pierre N., and others. “Memantine Treatment in Patients with Moderate to Severe Alzheimer Disease Already Receiving Donepezil: A Randomized Controlled Trial.” Journal of the American Medical Association 291 (2004): 317–24.
Winblad, Bengt, and others. “Donepezil in Patients with Severe Alzheimer’s Disease: Double-Blind, Parallel-Group, Placebo-Controlled Study.” Lancet 367.9516 (Apr. 2006): 1057–65.
Wong, Shelley. “The Safety of Donepezil in Treating Vascular Dementia.” CNS Spectrums 11.9 (Sept. 2006): 658–61.
OTHER
Eisai Co., Ltd. Aricept Prescribing Information. <http://www.aricept.com/content/pi.pdf>.
Kelly Karpa, R.Ph., PhD
Ruth A. Wienclaw, PhD
Donepezil
Donepezil
Definition
Donepezil is a drug used to treat dementia associated with Alzheimer's disease . In the United States, donepezil is sold under the brand name Aricept.
Purpose
Donepezil is used to help treat symptoms of Alzheimer's disease in individuals with mild to moderate illness. The drug may cause small improvements in dementia for a short period of time, but donepezil does not stop the progression of Alzheimer's disease.
Description
The Food and Drug Administration has approved donepezil for treatment of the symptoms of Alzheimer's disease. In Alzheimer's disease, some cells in specific regions of the brain die. Because of this cell death, these brain cells lose their ability to transmit nerve impulses. Brain cells normally transmit nerve impulses by secreting various chemicals known as neurotransmitters .
Brain cells that make and secrete a neurotransmitter called acetylcholine are affected early in the course of Alzheimer's disease. Donepezil helps prevent the breakdown of acetylcholine in the brain, thus temporarily increasing its concentration. In doing so, donepezil may improve the thinking process by facilitating nerve impulse transmission within the brain.
Donepezil is available as tablets in two different strengths. It is broken down by the liver.
Recommended dosage
The initial dosage of donepezil is 5 mg taken at bedtime. This dose should be continued for four to six weeks. The dosage may then be increased to 10 mg at bedtime, but there is no clear evidence that the higher dosage is more beneficial. However, the higher dosage is likely to cause more side effects.
Precautions
Donepezil may slow heart rate, increase acid in the stomach, make urination difficult, cause breathing difficulties, and may make it more likely for people to have seizures . As a result, it should be used carefully with close physician supervision by people with certain heart conditions, those who are prone to stomach ulcers, people with bladder obstruction, individuals with asthma or chronic obstructive pulmonary disease, and people with a history of seizure disorders.
People taking donepezil should be reassessed periodically to determine whether the drug is providing any benefits. When caregivers feel the drug is no longer beneficial, it may be stopped.
Side effects
More than 5% of people taking donepezil experience difficulty sleeping, dizziness, nausea, diarrhea, muscle cramps, headache, or other pains.
Diarrhea, nausea, and vomiting occur more often with the 10-mg dose than the 5-mg dosage. These adverse effects are usually mild, short-lived, and typically subside when the drug is stopped. Other, less common, side effects are abnormal dreams, depression, drowsiness, fainting, loss of appetite, weight loss, frequent urination, arthritis, and easy bruising.
Interactions
Many drugs may alter the effects of donepezil; likewise, donepezil may alter the action of other drugs. Drugs such as dicylomine, phenytoin, carbamazepine , dexamethasone, rifampin, or phenobarbital may lessen the effects of donepezil. Other drugs such as bethanechol, ketoconazole, or quinidine may increase some of the side effects associated with donepezil. When donepezil and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil) or naproxen are used together, there may be an increased tendency to develop stomach ulcers. Donepezil may increase the side effects associated with use of fluvoxamine , an antidepressant. If succinylcholine, a drug commonly used during anesthesia, is used with donepezil, prolonged muscle paralysis may result.
Resources
BOOKS
Eisai Co. Staff. Aricept Package Insert. Tokyo, Japan: Eisai Co. Ltd, 2000.
Facts and Comparisons Staff. Drug Facts and Comparisons. 6th Edition. St. Louis: Facts and Comparisons, 2002.
Mosby Staff. Mosby's Medical Drug Reference. St. Louis, MO: Mosby, Inc, 1999.
Kelly Karpa, RPh, Ph.D.