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Patients with moderate or severe Alzheimer’s disease who continued to worsen despite treatment with donepezil appeared to retain a small but significant benefit over those who added or switched to memantine or stopped taking medication for Alzheimer’s altogether in a randomized trial.
The patients in the 1-year study, DOMINO (Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease), who continued on donepezil (Aricept) showed improved cognitive and functional outcomes, compared with all other groups, Dr. Robert Howard of the Institute of Psychiatry, King’s College London, and his associates reported March 8 in the New England Journal of Medicine.
Patients who stopped donepezil and started memantine (Namenda) showed smaller but still significant benefits. Those who stopped donepezil and didn’t switch to memantine did not improve. And patients who continued donepezil and added memantine to their regimen did not improve further than those who simply continued donepezil.
However, "the improvements in cognition and function associated with donepezil and memantine were small relative to the overall size of the decline in cognitive and functional status that was seen in all patients," the investigators noted.
Noting that there is little evidence to guide the difficult decision regarding continuing or changing treatment when Alzheimer’s disease (AD) progresses, Dr. Howard and his colleagues studied 295 community-living patients with moderate or severe AD who had already taken donepezil for 2-3 years and whose clinicians were considering changing medication.
All the patients scored between 5 and 13 on the Standardized Mini-Mental State Examination (SMMSE), which ranges in score from 0 to 30; higher scores indicate better cognitive function. The investigators randomly assigned them to continue donepezil and start taking a placebo (73 patients), discontinue donepezil and start taking a placebo (73 patients), discontinue donepezil and start taking memantine (76 patients), or continue donepezil and start taking memantine (73 patients).
During a 1-year follow-up period, 137 (46%) withdrew from the trial, usually because of a perceived lack of benefit from continued treatment.
Compared with patients who discontinued donepezil, those who continued the drug scored better by 1.9 points on the SMMSE. They also scored better by 3 points on the 60-point, caregiver-rated Bristol Activities of Daily Living Scale (BADLS), indicating less functional impairment, the investigators said (N. Engl. J. Med. 2012;366:893-903).
Patients who began taking memantine scored a mean of 1.2 higher on the SMMSE and a mean of 1.5 points better on the BADLS, compared with patients who did not start the drug. However, combined treatment with the drugs did not provide any significant benefits beyond treatment with donepezil alone for any of the primary or secondary outcomes.
This study was funded by the U.K. Medical Research Council and the Alzheimer’s Society. Pfizer-Eisai and Lundbeck donated the drugs and placebos used in the study. Many of the authors reported financial ties to Pfizer and Eisai, which together market donepezil in the United States, as well as other companies that manufacture drugs for Alzheimer’s disease.
The study findings can be viewed in two ways. The patients, caregivers, and physicians who are reluctant to discontinue donepezil can take heart that the "small" improvement in SMMSE scores that occurred when patients continued taking donepezil is clinically important "because many of the patients were severely impaired, on the cusp for needing nursing home care, and slightly worse cognitive function could affect their ability to remain at home," Dr. Lon S. Schneider wrote.
On the other hand, Dr. Schneider noted that the results also support those who decide to discontinue donepezil by the fact that only half of the patients who were assigned to continue donepezil for the 1-year trial actually did so for the full year. That rate of withdrawal suggests "that many patients perceived that continuing medication was not effective."
The results of the trial do not amount to "evidence of the efficacy of indefinite treatment with donepezil" and also do not apply to the other cholinesterase inhibitors that have been approved for the treatment of Alzheimer’s disease, galantamine (Razadyne) and rivastigmine (Exelon), because of their different pharmacokinetics and mechanisms of cholinesterase inhibition, he wrote.
Lon S. Schneider, M.D., is in the department of psychiatry and behavioral sciences and the department of neurology at the University of Southern California, Los Angeles. He reported ties to Forest Laboratories (which markets memantine in the United States), Pfizer, Wyeth, Novartis, Johnson & Johnson, and Merz and Lundbeck (which together market memantine outside of the United States). These remarks were taken from his editorial accompanying Dr. Howard’s report (N. Engl. J. Med. 2012;366:957-9).
The study findings can be viewed in two ways. The patients, caregivers, and physicians who are reluctant to discontinue donepezil can take heart that the "small" improvement in SMMSE scores that occurred when patients continued taking donepezil is clinically important "because many of the patients were severely impaired, on the cusp for needing nursing home care, and slightly worse cognitive function could affect their ability to remain at home," Dr. Lon S. Schneider wrote.
On the other hand, Dr. Schneider noted that the results also support those who decide to discontinue donepezil by the fact that only half of the patients who were assigned to continue donepezil for the 1-year trial actually did so for the full year. That rate of withdrawal suggests "that many patients perceived that continuing medication was not effective."
The results of the trial do not amount to "evidence of the efficacy of indefinite treatment with donepezil" and also do not apply to the other cholinesterase inhibitors that have been approved for the treatment of Alzheimer’s disease, galantamine (Razadyne) and rivastigmine (Exelon), because of their different pharmacokinetics and mechanisms of cholinesterase inhibition, he wrote.
Lon S. Schneider, M.D., is in the department of psychiatry and behavioral sciences and the department of neurology at the University of Southern California, Los Angeles. He reported ties to Forest Laboratories (which markets memantine in the United States), Pfizer, Wyeth, Novartis, Johnson & Johnson, and Merz and Lundbeck (which together market memantine outside of the United States). These remarks were taken from his editorial accompanying Dr. Howard’s report (N. Engl. J. Med. 2012;366:957-9).
The study findings can be viewed in two ways. The patients, caregivers, and physicians who are reluctant to discontinue donepezil can take heart that the "small" improvement in SMMSE scores that occurred when patients continued taking donepezil is clinically important "because many of the patients were severely impaired, on the cusp for needing nursing home care, and slightly worse cognitive function could affect their ability to remain at home," Dr. Lon S. Schneider wrote.
On the other hand, Dr. Schneider noted that the results also support those who decide to discontinue donepezil by the fact that only half of the patients who were assigned to continue donepezil for the 1-year trial actually did so for the full year. That rate of withdrawal suggests "that many patients perceived that continuing medication was not effective."
The results of the trial do not amount to "evidence of the efficacy of indefinite treatment with donepezil" and also do not apply to the other cholinesterase inhibitors that have been approved for the treatment of Alzheimer’s disease, galantamine (Razadyne) and rivastigmine (Exelon), because of their different pharmacokinetics and mechanisms of cholinesterase inhibition, he wrote.
Lon S. Schneider, M.D., is in the department of psychiatry and behavioral sciences and the department of neurology at the University of Southern California, Los Angeles. He reported ties to Forest Laboratories (which markets memantine in the United States), Pfizer, Wyeth, Novartis, Johnson & Johnson, and Merz and Lundbeck (which together market memantine outside of the United States). These remarks were taken from his editorial accompanying Dr. Howard’s report (N. Engl. J. Med. 2012;366:957-9).
Patients with moderate or severe Alzheimer’s disease who continued to worsen despite treatment with donepezil appeared to retain a small but significant benefit over those who added or switched to memantine or stopped taking medication for Alzheimer’s altogether in a randomized trial.
The patients in the 1-year study, DOMINO (Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease), who continued on donepezil (Aricept) showed improved cognitive and functional outcomes, compared with all other groups, Dr. Robert Howard of the Institute of Psychiatry, King’s College London, and his associates reported March 8 in the New England Journal of Medicine.
Patients who stopped donepezil and started memantine (Namenda) showed smaller but still significant benefits. Those who stopped donepezil and didn’t switch to memantine did not improve. And patients who continued donepezil and added memantine to their regimen did not improve further than those who simply continued donepezil.
However, "the improvements in cognition and function associated with donepezil and memantine were small relative to the overall size of the decline in cognitive and functional status that was seen in all patients," the investigators noted.
Noting that there is little evidence to guide the difficult decision regarding continuing or changing treatment when Alzheimer’s disease (AD) progresses, Dr. Howard and his colleagues studied 295 community-living patients with moderate or severe AD who had already taken donepezil for 2-3 years and whose clinicians were considering changing medication.
All the patients scored between 5 and 13 on the Standardized Mini-Mental State Examination (SMMSE), which ranges in score from 0 to 30; higher scores indicate better cognitive function. The investigators randomly assigned them to continue donepezil and start taking a placebo (73 patients), discontinue donepezil and start taking a placebo (73 patients), discontinue donepezil and start taking memantine (76 patients), or continue donepezil and start taking memantine (73 patients).
During a 1-year follow-up period, 137 (46%) withdrew from the trial, usually because of a perceived lack of benefit from continued treatment.
Compared with patients who discontinued donepezil, those who continued the drug scored better by 1.9 points on the SMMSE. They also scored better by 3 points on the 60-point, caregiver-rated Bristol Activities of Daily Living Scale (BADLS), indicating less functional impairment, the investigators said (N. Engl. J. Med. 2012;366:893-903).
Patients who began taking memantine scored a mean of 1.2 higher on the SMMSE and a mean of 1.5 points better on the BADLS, compared with patients who did not start the drug. However, combined treatment with the drugs did not provide any significant benefits beyond treatment with donepezil alone for any of the primary or secondary outcomes.
This study was funded by the U.K. Medical Research Council and the Alzheimer’s Society. Pfizer-Eisai and Lundbeck donated the drugs and placebos used in the study. Many of the authors reported financial ties to Pfizer and Eisai, which together market donepezil in the United States, as well as other companies that manufacture drugs for Alzheimer’s disease.
Patients with moderate or severe Alzheimer’s disease who continued to worsen despite treatment with donepezil appeared to retain a small but significant benefit over those who added or switched to memantine or stopped taking medication for Alzheimer’s altogether in a randomized trial.
The patients in the 1-year study, DOMINO (Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease), who continued on donepezil (Aricept) showed improved cognitive and functional outcomes, compared with all other groups, Dr. Robert Howard of the Institute of Psychiatry, King’s College London, and his associates reported March 8 in the New England Journal of Medicine.
Patients who stopped donepezil and started memantine (Namenda) showed smaller but still significant benefits. Those who stopped donepezil and didn’t switch to memantine did not improve. And patients who continued donepezil and added memantine to their regimen did not improve further than those who simply continued donepezil.
However, "the improvements in cognition and function associated with donepezil and memantine were small relative to the overall size of the decline in cognitive and functional status that was seen in all patients," the investigators noted.
Noting that there is little evidence to guide the difficult decision regarding continuing or changing treatment when Alzheimer’s disease (AD) progresses, Dr. Howard and his colleagues studied 295 community-living patients with moderate or severe AD who had already taken donepezil for 2-3 years and whose clinicians were considering changing medication.
All the patients scored between 5 and 13 on the Standardized Mini-Mental State Examination (SMMSE), which ranges in score from 0 to 30; higher scores indicate better cognitive function. The investigators randomly assigned them to continue donepezil and start taking a placebo (73 patients), discontinue donepezil and start taking a placebo (73 patients), discontinue donepezil and start taking memantine (76 patients), or continue donepezil and start taking memantine (73 patients).
During a 1-year follow-up period, 137 (46%) withdrew from the trial, usually because of a perceived lack of benefit from continued treatment.
Compared with patients who discontinued donepezil, those who continued the drug scored better by 1.9 points on the SMMSE. They also scored better by 3 points on the 60-point, caregiver-rated Bristol Activities of Daily Living Scale (BADLS), indicating less functional impairment, the investigators said (N. Engl. J. Med. 2012;366:893-903).
Patients who began taking memantine scored a mean of 1.2 higher on the SMMSE and a mean of 1.5 points better on the BADLS, compared with patients who did not start the drug. However, combined treatment with the drugs did not provide any significant benefits beyond treatment with donepezil alone for any of the primary or secondary outcomes.
This study was funded by the U.K. Medical Research Council and the Alzheimer’s Society. Pfizer-Eisai and Lundbeck donated the drugs and placebos used in the study. Many of the authors reported financial ties to Pfizer and Eisai, which together market donepezil in the United States, as well as other companies that manufacture drugs for Alzheimer’s disease.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Major Finding: Compared with patients who stopped taking donepezil, those who continued the drug scored better by 1.9 points on the SMMSE and by 3.0 points on the BADLS.
Data Source: The 1-year randomized, controlled trial compared outcomes in 295 community-dwelling patients with AD who followed four different drug regimens containing donepezil, memantine, or placebo.
Disclosures: This study was funded by the U.K. Medical Research Council and the Alzheimer’s Society. Pfizer-Eisai and Lundbeck donated the drugs and placebos used in the study. Dr. Howard reported ties to Pfizer-Eisai and Lundbeck, and his associates reported ties to numerous industry sources.