Aricept (donepezil hydrochloride tablets)
Cheryl Nichols
Table of Contents
What is Alzheimer’s disease?
Alzheimer’s
disease is a disease in which the memory, judgment, and thought processes are
impaired. The moods and personality of
a sufferer may also be affected. The symptoms
may progress slowly and come-and-go. (http://www.healingwell.com/alzheimers/info.htm)
This
disease affects the cholinergic functions in the brain. It causes a deficiency of cholinergic neuron
transmission. Thus, the memory of the
Alzheimer’s patient is impaired. The
drug donepezil hydrochloride enhances the cholinergic functions. As the amount of functioning neurons
decreases, the drug’s effectiveness decreases. (http://pfizer.com/hml/pi’s/ariceptpi.html)
What is
Aricept?
Aricept
is a drug used to treat Alzheimer’s disease.
It is available in tablet form and is considered to be in the drug
sub-class of an acetylcholin-esterase inhibitor. Patients should start taking 5 mg of Aricept at bedtime. After four to six weeks, the dose can be
increased to 10 mg/day. It is used to
decrease the mild to moderate symptoms of the disease in an effort to reverse,
reduce, or retard the mental and behavioral process of dementia. Aricept is not a cure for the disease, but
it is a way to make it more manageable. (http://www.mayohealth.org/mayo/9804/htm/alztreat.htm)
How does
it work?
Aricept is also known as donepezil
hydrochloride and E2020. It is a
reversible inhibitor of the enzyme acetyl cholinesterase, and has an empirical formula
of C24H29NO3HCL
. 
(pic. from Pfizer)
The donepezil hydrochloride enhances cholinergic function by
increasing acetylcholine though it’s inhibiting of acetyl cholinesterase. This effect is thought to lessen as the
disease advances because fewer cholinergic neurons are functioning. Thus, donepezil does not alter the course of
the dementing process; it just makes the dementia more tolerable. (http://pfizer.com/hml/pi’s/ariceptpi.html)
Is it
effective?
Aricept
has been determined to be an effective treatment during its use. This is proved by the various clinical
studies.
The
people at Pfizer Incorporated studied Aricept to determine if it was an
effective treatment for Alzheimer’s disease.
They conducted two randomized, double blind, placebo-controlled clinical
investigations with Alzheimer’s patients.
The ages of the participants ranged from 50 to 94 with a mean age of
73. The participants were 62% women and
38% men. Of these groups, 95% were
white, 3% were black, and 2% were other races.
The effectiveness of the drug was measured using the Alzheimer’s
Assessment Scale (ADAS-cog) and the Clinician’s Interview Based Impression of
Change (CIBIC plus).
The
ADAS-cog is a scale of approximately 26 units ranging from 4 to 61. Studies have shown that mild to moderate
Alzheimer’s sufferers gain 6 to 12 units a year on the ADAS-cog, but very mild
or advanced sufferers show less change because the ADAS-cog is not sensitive to
the change over the course of the disease.
The
CIBIC plus examines the General, Cognitive, Behavioral, and Activities of Daily
Living. It is the assessment by a
clinician after an interview with the patient combined with the information
from a caregiver. The scores are
divided into seven categories. One
indicates “markedly improved,” four indicates “no change,” and seven indicates
“markedly worse.”
The
first study conducted by Pfizer Incorporated was a thirty-week study in which
patients randomly received daily doses of placebo, 5mg/day, or 10 mg/day of
Aricept. The 10-mg/day-treatment group
started after 7 days of treatment with 5 mg/day. The double blind active treatment phase lasted for 24 weeks and
was followed by a 6-week single blind washout period.
After
24 weeks of treatment, the ADAS-cog change scores were 2.8 and 3.1 units for
the 5 and 10 mg/day groups in comparison with the placebo group. The mean drug-placebo differences on the
CIBIC plus were 0.35 units and 0.39 units for the 5 and 10 mg/day groups in
comparison. After the 6-week placebo
washout period, the scores of the Aricept groups were the same as the placebo
group. This proves that Aricept does
not cure the disease.
Fig.1
Fig.2
Fig 1: Time-course of the Change from Baseline in ADAS-cog
Score for Patients Completing 24 Weeks of Treatment (drawing by Pfizer)
Fig 2: Frequency Distribution of CIBIC
plus Scores at Week 24 (drawing by Pfizer)
The
second study by Pfizer Incorporated was a 15-week study. Two groups received 5 mg/day or 10 mg/day of
Aricept, and another group received a placebo.
This lasted for 12 weeks with a 3-week placebo washout period. After 12 weeks of treatment, the Aricept
treatment groups changed by 2.7 and 3.0 units on the ADAS-cog. On the CIBIC plus, the differences were 0.36
and 0.38 units in the treatment groups after 12 weeks. After the 3-week placebo washout, the scores
for the groups increased because the washout period duration was not long
enough to predict the loss of treatment effect.
Fig. 3
Fig.4
Fig. 3: Time-course of the Change from
Baseline in ADAS-cog Score for Patients Completing the 15-Week Study (drawing
by Pfizer).
Fig. 4: Frequency Distribution of
CIBIC plus Scores at Week 12. (drawing by Pfizer)
(http://pfizer.com/hml/pi’s/ariceptpi.html)
Another
study on the effects of Aricept was presented at the 50th annual
meeting of the American Academy of Neurology.
Larry E. Tune, M.D., a professor at the Emory Center on Aging in Atlanta
and chief of Geriatric Psychiatry at Wesley Woods Hospital in Atlanta conducted
it. This study’s goal was to prove a
change in the functional activity of the brain of a patient taking Aricept
using the PET technique.
PET measures the cerebral glucose
metabolism using radioactively labeled tracers. This technique can estimate the glucose metabolism in whole
sections or in regions of interest. PET
studies have shown that a reduction in cerebral glucose metabolism is linked
with Alzheimer-type dementia.
Dr.
Tune’s study was a 24-week double blind study in which PET was used to measure
the cerebral glucose metabolism of mild to moderate Alzheimer’s patients taking
10 mg/day of Aricept. At the end of the
study, no apparent changes in global functional brain activity occurred in the
Aricept patients. However, the
placebo-treated patients’ global functional brain activity declined by 9-10
percent. This study shows that Aricept
patients experience retention of cerebral glucose metabolism. (http://dem0nmac.mgh.harvard.edu/forum/AlzheimersDiseaseF/4.30.982.23PMAlzheimersAricept)
In
a study by Rogers et al. (1999) published in the Dementia Cognitive Disorders
Journal, the effects of donepezil in the treatment for Alzheimer’s disease was
researched. This study was a 30-week,
placebo-controlled, parallel group study.
The actual treatment was given for 24 weeks, and it was followed by a
6-week placebo washout. It included 818
patients with mild to moderately severe Alzheimer’s disease were given either
single daily doses of 5 or 10 mg of donepezil, or a placebo. These treatments were assigned to the group
randomly. After the treatment, the
patients were given various tests to determine the drug’s effectiveness. In the 5 and 10mg/day groups, there was a
significant improvement in cognitive and global functions as compared to the
placebo group. These results confirm
that donepezil is effective in treating Alzheimer’s disease. In a second study done by Friedhoff and Rogers
(1998) in the Neurology Journal, the effectiveness and safety of donepezil was
analyzed. This was a multicenter,
double blind study with patients randomly assigned to treatment groups. The treatments were 5 mg/day of donepezil,
10 mg/day, or a placebo. This was a
24-week study with a 6-week washout period.
The patients were tested after the treatments, and the donepezil groups
increased cognitive and global ratings.
Side effects, such as diarrhea, nausea, and vomiting were more prevalent
in the 10-mg/day group. As in the
previous study, this proves that donepezil is a well-tolerated drug for
Alzheimer’s disease treatment.
Conclusion
Aricept
is a good treatment for Alzheimer’s sufferers.
It enhances the function of the active neurons in the brain. The various studies show that it is
effective in improving memory. This
treatment can be used to maintain the person’s normal functions, but it cannot
stop the process as the condition worsens.
The disease can progress slowly, and the use of Aricept can be helpful
in the mild to moderate levels of the disease.
References
1) Burns, A., Friedhoff, L. T., Gauthier,
S., Hecker, J., Moller, H. J., Petit, H., Rogers, S. L., Rossor, M. (1999). The effects of donepezil in Alzheimer’s
disease-results from a multinational trial. Geriatric Cognitive Disorders,
10(3), 237-44.
2) Friedhoff, L. T., Rogers, S. L.
(1998). A 24-week double blind, placebo-controlled trial of donepezil in patients
with Alzheimer’s disease. Neurology, 50(1), 136-45. )
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