Aricept (donepezil hydrochloride tablets)

Cheryl Nichols

Table of Contents

What is Alzheimer’s disease?

What is Aricept?

How does it work?

Is it effective?

Conclusion

References

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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