Other studies: Eisai’s Aricept, Alzheimer’s Rivals Fail to Get Wider
U.K. Use http://www.bloomberg.com/apps/news?pid=newsarchive&sid=a2_KzCCiOa4Q
finds same as one below: http://www.worstpills.org/member/newsletter.cfm?n_id=753
High doses of Alzheimer's drug Aricept should be banned, Public Citizen says
Los Angeles Times at http://articles.latimes.com/2011/may/18/news/la-heb-alzheimers-aricept-05182011
May 18, 2011 By Thomas
H. Maugh II, Los Angeles Times/For the Booster Shots blog
High doses of the Alzheimer's drug Aricept should be banned because they are no more effective than low doses and have a sharply increased risk of adverse effects, the advocacy group Public Citizen and a Johns Hopkins University geriatrician said
Wednesday in a petition to the Food and Drug Administration. Aricept, known generically as donepezil, is one of the very few
drugs available for treating Alzheimer's disease, but it provides only a very modest slowing in the cognitive and functional
deficits associated with the disease. Yet the drug is widely used "due primarily to two factors: the understandable desperation
of those who care for patients with Alzheimer's disease and a relentless promotional campaign by drug companies," said co-petitioner
Dr. Thomas Finucane of Hopkins.
Aricept has been approved by
the FDA in dosages of 5 to 10 milligrams for patients with mild to moderate cases of Alzheimer's and in a dose of 10 to 23
milligrams for more severe cases. The petition asks the FDA to ban
the 23-mg version of the drug and to warn patients and physicians against taking two 10-mg. pills per day if the higher dosage
is removed from the market.
Clinical trials of Aricept
submitted to the FDA for approval show no significant benefit from the 23-mg version compared to the 10-mg version, the petition
said. But the increased adverse effects from the higher dosage include a slowed pulse rate, nausea, vomiting, diarrhea, urinary
incontinence, fatigue, dizziness, agitation, confusion and anorexia. Vomiting, which occurred more than 3 1/2 times more frequently
in those taking the high dosage, is a particularly dangerous side effect for Alzheimer's patients, the petition says, because
it can lead to pneumonia, massive gastrointestinal bleeding, esophageal rupture and even death.
"With no evidence of an added
advantage in benefit to patients, the clear increase in risk should have been more than adequate grounds for denying approval,"
said Dr. Sidney Wolfe, director of Public Citizen's Health Research Group. "It is inexcusable that FDA approved this higher
dose. Its prompt removal would belatedly fulfill the agency's mission to allow only drugs whose benefits outweigh their risks
to be marketed."
Public Citizen has a long history
of campaigning against drugs that it considers dangerous or ineffective.
Since the review committees of our medical journals
do not receive the raw data, the marketing departments of pharmaceutical companies and their paid researchers can and do manipulate
the data so as to free distort the results of the articles submitted for publication in a positive way. The article
below is a review of the raw, obtained from the Freedom of Information Act, and a positive bias average 32%. Raw data
is not presented with the articles submitted to journals.
There is a fundamental
conflict of interest for the journals because their principle source of revenue is from the advertisers who submit the articles.
Moreover, every significant medical journal has been purchased by a corporation—50 years ago they were affiliated with principle medical schools. Thus there is strong
incentive not to look too critically at what has been submitted. For a in-depth accounting of how PhARMA manipulates
the product of drug information read Professor Marcia Angell’s book The Truth About Drug Companies: How They Deceive US and What to Do About It. The average
positive bias found in a NEJM study using raw data, obtain through the Freedom of Information Act, was 32%. A drug only has to be better than a placebo for approval for the condition
treated, and many are worse than no treatment when considering the side effects (see for the article Volume 358:252-260, January
17, 2008, Number 3
http://content.nejm.org/cgi/content/short/358/3/252 -- jk.
Published Online: 21 JAN 2009, Assessed as up-to-date: 14 SEP 2005, DOI: 10.1002/14651858.CD005593
Cholinesterase inhibitors for Alzheimer's disease
Since the introduction of the first cholinesterase inhibitor
(ChEI) in 1997, most clinicians and probably most patients would consider the cholinergic drugs, donepezil, galantamine and
rivastigmine, to be the first line pharmacotherapy for mild to moderate Alzheimer's disease.
The drugs have slightly different pharmacological properties,
but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking
the enzyme acetylcholinesterase. The most that these drugs could achieve is to modify the clinical manifestations of Alzheimer's
disease. Cochrane reviews of each ChEI for Alzheimer's disease have been completed.
To assess the effects of donepezil, galantamine and
rivastigmine in people with mild, moderate or severe dementia due to Alzheimer's disease.
The Cochrane Dementia and Cognitive Improvement Group's
Specialized Register was searched using the terms 'donepezil', 'E2020' , 'Aricept' , galanthamin* galantamin* reminyl, rivastigmine,
exelon, "ENA 713" and ENA-713 on 12 June 2005. This Register contains up-to-date records of all major health care databases
and many ongoing trial databases.
All unconfounded, blinded, randomized trials of at least
six months in which treatment with a ChEI at the usual recommended dose was compared with placebo or another ChEI for patients
with mild, moderate or severe dementia due to Alzheimer's disease.
Data collection and analysis
Data were extracted by one reviewer (JSB), pooled where
appropriate and possible, and the pooled treatment effects, or the risks and benefits of treatment, estimated.
The results of 10 randomized, double blind, placebo
controlled trials demonstrate that treatment for 6 months, with donepezil, galantamine or rivastigmine at the recommended
dose for people with mild, moderate or severe dementia due to Alzheimer's disease produced improvements in cognitive function, on average
-2.7 points (95%CI
-3.0 to -2.3, p<0.00001), in the midrange of the 70 point ADAS-Cog Scale. Study clinicians rated global clinical state
more positively in treated patients. Benefits of treatment were also seen on measures of activities of daily living and behaviour. None
of these treatment effects are large.
The effects are similar for patients with severe dementia,
although there is very little evidence, from only two trials.
More patients leave ChEI treatment groups, 29%, on account
of adverse events than leave the placebo groups (18%).
There is evidence of more adverse events in total in
the patients treated with a ChEI than with placebo. Although many types of adverse event were reported, nausea, vomiting, diarrhoea, were significantly more frequent
in the ChEI groups than in placebo.
There is only one randomized, double blind study in
which two ChEIs are compared, donepezil compared with rivastigmine.
There is no evidence of a difference between
donepezil and rivastigmine for cognitive function, activities of daily living and behavioural disturbance at two years. Fewer
patients suffer adverse events on donepezil than rivastigmine.
The three cholinesterase inhibitors are efficacious
for mild to moderate Alzheimer's disease. Despite the slight variations in the mode of action of the three cholinesterase
inhibitors there is no evidence of any differences between them with respect to efficacy. The evidence from one large trial
shows fewer adverse events associated with donepezil compared with rivastigmine.