Banned drug can reverse Alzheimer's disease

A drug that has been banned from the NHS can reverse the effects of Alzheimer's disease in the worst affected patients, researchers have discovered.

In the first trial of the drug, donepezil, in the treatment of severe dementia, doctors found it improved cognition and the ability to carry out daily activities among patients cared for in nursing homes.

The finding, published in the online edition of The Lancet, will increase pressure on the National Institute of Health and Clinical Excellence (Nice) to revise its decision to ban the drug.

Nice, the Government watchdog that monitors the cost and effectiveness of medicines and treatments, has been reviewing drugs that combat Alzheimer's disease since 2004.

The disease affects an estimated 500,000 people in the UK and is a degenerative condition that erodes sufferers' ability to think and function and strips them of their personality.

Three drugs known as cholinesterase inhibitors including donepezil, whose brand name is Aricept, have been shown by research to slow the progression of disease in some patients.

However, in preliminary guidance issued in March 2005 that caused a storm of protest, Nice concluded that the drugs were not cost-effective and should be banned on the NHS.

Donepezil and its sister drugs cost about £2.50 a day but only one in five patients benefit and it is impossible to tell in advance which patients these will be, researchers say.

The recommendation, which was in draft form for consultation, triggered the biggest protest in Nice's history. About 8,000 responses were received, of which only one was in support of the decision.

In revised draft guidance issued in January this year, NIice relaxed its hard-line stance and proposed the drugs be made available to patients with moderate Alzheimer's disease, where they were most effective, but should still be denied to those in the early and late stages of the disease.

The Alzheimer's Disease Society said the guidance was unethical, lacked clinical sense and put doctors in an impossible position.

"Their patients have got to get worse before they can prescribe drugs designed to stop them getting worse," a spokesman said.

The consultation period on the recommendation has now closed and Nice is to meet on 27 April to consider the final determination. They have asked the manufacturers of the drugs for evidence suggesting how patients who might benefit from them could be identified.

The study, conducted by doctors from the Karolinska Institute, Sweden, will add to the pressure on Nice to reconsider. The researchers compared the effect of donepezil in 99 patients who were given the drug for six months with 95 patients given a placebo.

After six months, those who took donepezil showed significant improvement compared with those on placebo, and suffered few side-effects. The patients were aged over 50 and were recruited from 50 nursing homes in Sweden. All had severe dementia which affects one in five of those with Alzheimer's disease.

"Our findings indicate donepezil can improve cognition and preserves function in patients with severe Alzheimer's disease," the researchers wrote.

A concern of Alzheimer's researchers is that drug treatments may prolong survival in a demented state and thus unnecessarily prolong suffering.

In what campaigners will cite as a direct challenge to Nice, the researchers say: "Sustained use of cholinesterase inhibitors is not associated with any survival advantage. Thus, if treatment can help patients in the late phase of dementia, without necessarily increasing the length of time they have severe Alzheimer's disease, then this is a treatment option that should be available."

However, a commentary on the research published in The Lancet says treatment for people with severe dementia is "a case of too little too late."

David Hogan of the University of Calgary Health Sciences Centre, Canada, said it was unclear whether the improvements that the researchers noted were clinically important. "To most doctors, these outcome measures are numbers without meaning ... More meaningful outcome measures are needed in dementia trials," he writes.

Susanne Sorensen, head of research at the Alzheimer's Disease Society, said: "It is ironic that while more evidence is emerging of the effectiveness of drug treatments for Alzheimer's disease, Nice is threatening to restrict their use because of cost."

"While improvements in people in the later stages of the disease on Aricept are sometimes small, these changes can make an enormous difference to a person's life. It can mean being able to indicate when you are hungry or thirsty or increase a person's mobility, preventing bedsores. People should be given the opportunity to try the drugs."

The search for a cure

* February 1997 - Donepezil, first of the drugs for Alzheimer's, is licensed for use in the UK

* Studies show that the cholinesterase inhibitors - donepezil, galantamine, rivastigmine - are effective in slowing the progression of early to moderate Alzheimer's disease in some patients

* January 2001 - Nice recommends the drugs should be prescribed on the NHS at an estimated cost of £1,000 per person

* 2003 - Nice begins a new review of the Alzheimer's drugs in the light of new evidence

* 1 March 2005 - First draft guidance banning use of the drugs on the NHS on the grounds that they are not cost-effective

* 9 March 2005 - The Royal College of Psychiatrists condemns the decision saying it will have a "detrimental effect on the health and lives of patients and their carers"

* July 2005 - Nice defers its decision on the draft guidance after being overwhelmed by 8,000 mainly negative responses

* January 2006 - Nice issues a set of revised draft guidance, saying the drugs should be prescribed on the NHS to people with moderate Alzheimer's disease but should remain banned in those with early and late stage disease, on cost effectiveness grounds

* 27 April 2006 - Nice is due to meet to consider outcome of consultation on latest draft guidance

* Summer 2006 - Nice is scheduled to issue its final determination on the use of Alzheimer's drugs on the NHS.