Alzheimer's Drug, Aricept avoid

GERIATRIC ISSUES

Alzheimer's Drug, Aricept avoid

In 2006 NICE (the board that guides NIH in the UK as to approved medications reversed its 2001position on Aricept, (donepezil) Exelon (rivastigmine, and Reminyl (galantamine), all choleinesterase inhibitors, as to use for mild to moderate Alzheimer’s (it was never indicated for severe Alzheimer’s). The drug is barely better than a sugar pill on memory tests for Alzheimer’s patients. The Worstpill.com article supports this. Given the side effects it never should have been considered.

In general Alzheimer’s drugs are not worth using. The low hurdle of better than a placebo, and permitting short-term studies (often 6 weeks) has permitted a number of drugs who are barely better than a placebo for improving cognitive function, but who health consequence including shortening life make it not worth taking. Aricept is one of those drugs. There are no treatments, even modestly effective for Alzheimer’s.

Fortunately both hormones (estrogen and testosterone) and aspirin very significantly lower the risk. (use the Google search on the home page to find such articles). The reason for the rise in Alzheimer’s in the last 40 years is PhARMA’s getting the public away from the standard over-the-counter drug aspirin, and their teaching doctors not to give estrogen to post-menopausal women—don’t deliberately on bad science. Estrogen lowers risk up to 83%, aspirin up to 60%, and I have yet to research articles on just how much testosterone lowers Alzheimer’s.

http://www.worstpills.org/member/newsletter.cfm?n_id=753

Remove Dangerous Alzheimer’s Drug -- ARICEPT 23 -- From the Market Immediately

Worst Pills Best Pills Newsletter article July, 2011

{For a look at the science behind this go to The petition}

A drug used to treat moderate or severe cases of Alzheimer’s disease should be removed from the market immediately because of its risk of serious adverse effects and its lack of effectiveness, Public Citizen and an eminent geriatrician from Johns Hopkins said in a recent petition filed with the Food and Drug Administration (FDA).

Donepezil, also known as ARICEPT, has been approved by the FDA in a dose of 5 to 10 milligrams (mg) for patients with mild to moderate cases of Alzheimer’s disease and in a dose of 10 or 23 mg (ARICEPT 23)for patients with moderate to severe Alzheimer’s.

Data show that the 23-mg dose of donepezil, approved last July, is significantly more toxic than the 10-mg dose. Combined with its lack of improved clinical benefits, this leads to only one conclusion: that the 23-mg dose should be immediately withdrawn from the market.

We are also asking the FDA to warn doctors and patients against taking 20 mg of the drug (two 10-mg pills) a day, even if ARICEPT 23 is removed from pharmacy shelves.

Dr. Thomas Finucane, professor of medicine in the Division of Gerontology and Geriatric Medicine at the Johns Hopkins University School of Medicine and staff physician at the Johns Hopkins Bayview Medical Center, stated that “Cholinesterase inhibitors such as ARICEPT have gained multibillion-dollar success 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.” Finucane is a co-petitioner with Public Citizen to ban ARICEPT 23.

“When clinicians consider whether to initiate a therapeutic trial of a largely ineffective drug, the risk of harm should be a prominent consideration,” Finucane said. “The clearly increased risk of harm from ARICEPT 23-mg compared to ARICEPT 10-mg is so great, coupled with the lack of any evidence of improved benefit, that I believe it should not have been approved for sale to the families and caregivers of Alzheimer patients.”

The only clinical trial of donepezil submitted to the FDA for approval of the 23-mg dose compared it to the 10-mg dose and failed to prove that the higher dose was more effective. In three of four tests, on either a cognitive or functional level, there was no significant difference between the 10- and 23-mg doses. In the fourth test, the improvement over the 10-mg dose was only two points on a 100-point scale, which is not clinically important.

Increased adverse effects of the 23-mg dose of donepezil compared to the 10-mg dose include a slowed pulse rate, nausea, vomiting, diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion and loss of appetite. Vomiting — which occurred more than 3.5 times as often in patients taking the 23-mg dose than those taking the 10-mg dose — is a particularly dangerous side effect for patients with Alzheimer’s disease because it can lead to pneumonia, massive gastrointestinal bleeding, esophageal rupture and even death. Overall, patients taking the 23-mg dose stopped taking the drug because of adverse effects more than twice as often as those taking the 10-mg dose. Additionally, because of the drug’s very long half-life, it can stay in patients’ systems for about two weeks after they stop taking the drug. So those who suffered adverse effects may not have immediate relief after they stop treatment.

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, a conclusion reached by both the FDA medical officer and statistician. It is inexcusable that the FDA approved this higher dose. Its prompt removal would belatedly fulfill the agency’s mission to allow the marketing of only those drugs whose benefits outweigh their risks.

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

Worstpills article finds same as one below: http://www.worstpills.org/member/newsletter.cfm?n_id=753

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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.

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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

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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

Abstract

Background

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.

Objectives

To assess the effects of donepezil, galantamine and rivastigmine in people with mild, moderate or severe dementia due to Alzheimer's disease.

Search methods

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.

Selection criteria

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.

Main results

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.

Authors' conclusions

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.