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Title: Tacrine Slows Cognitive Deterioration For Alzheimer's Patients
URL: http://www.pslgroup.com/dg/C5DBE.htm
Doctor's Guide
November 24, 1998


CHICAGO, IL -- Nov. 24, 1998 -- The drug tacrine hydrochloride appears to have an overall beneficial, but small, effect on cognitive performance for Alzheimer's patients, according to an article in tomorrow's issue of The Journal of the American Medical Association.

Nawab Qizilbash, formerly with the Dementia Trialists' Collaboration at the University of Oxford in England, and colleagues analysed data from 12 randomised, double-blind, placebo-controlled trials involving a total of 1,284 patients with Alzheimer disease (AD).

AD is a progressive condition in which nerve cells degenerate in the brain, causing those affected to progressively lose their memory. AD is responsible for about 75 percent of dementia cases in people over the age of 65.

"Cholinesterase inhibition with tacrine appears to reduce deterioration in cognitive performance for more than three months and increase the odds of global clinical improvement," they write. "The effect on Clinical Global Impressions of change suggests that tacrine can produce clinically observable differences in overall conduct, behaviour and function.

"The odds of improving when taking tacrine compared with placebo increased by about 50 percent and the number of patients needed to treat to show any improvement was 11, while the number needed to treat for a moderate or marked improvement was 42."

However, one patient withdrew for every four patients who were treated with tacrine because of adverse effects from the drug.

"Effects observed on measures of behavioural disturbance were of questionable clinical significance and functional autonomy was not significantly affected," they write. "The relevance of the benefits of cholinesterase inhibition remains controversial and long-term trials with clinically relevant end points are required."

The researchers conducted a meta-analysis to determine the effects of tacrine hydrochloride on cognitive performance, clinical global impression, behaviour and functional autonomy among Alzheimer's patients. Tacrine belongs to a class of drugs known as cholinesterase inhibitors. It was the first drug to be widely marketed to treat the symptoms of Alzheimer disease. But its efficacy remains controversial and several countries have refused to approve its use.

The authors analysed data from 12 trials involving tacrine doses ranging from 20 milligrams per day to 160 milligrams per day. Treatment duration ranged from three to 26 weeks. Times and frequencies of assessment also varied among the trials. For the meta-analysis, the effect of tacrine compared to placebo was measured at 12 weeks.

Among the other conclusions of the meta-analysis:
-- The average final daily dose from each study showed no significant evidence of a greater treatment effect with increasing dose.
-- Men appeared to benefit more from tacrine than women.
-- Previous suggestions that tacrine is more effective in patients with mild disease, moderate disease and in older patients were not supported by the meta-analysis.
-- Since only two of the 12 trials had assessments after 12 weeks, it was not possible to make reliable estimates of the effects of tacrine beyond that point.

"Efforts should continue to be directed toward further defining the types of patients and the circumstances in which they may benefit from newer cholinesterase inhibitors, prospectively defining subgroups to assess response and using better measures of important functional and behavioural outcomes," they said. "Addressing these issues reliably requires much larger trials, ideally all using a common core set of assessments of behaviour and function, as well as cognition and Clinical Global Impression of change.

"Furthermore, none of the cholinesterase inhibitors have reliable controlled data on meaningful outcomes such as dependency and institutionalisation or other aspects of long-term efficacy. Such trials are urgently needed."

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