Alzheimer's Sufferers Could Benefit From Memantine And Donepezil In Later Stages Of Disease

Alzheimer's Sufferers Could Benefit From Memantine And Donepezil In Later Stages Of Disease

Hundreds of thousands more people in the UK with Alzheimer's disease could benefit from two key drugs, research suggests.

Experts found that memantine and in particular donepezil could help ease symptoms in the later stages of the disease, not just earlier on.

Donepezil, which is the most commonly used dementia drug in the UK, is currently approved for use on the NHS for mild to moderate stages of the disease.

It works by increasing the amount of a neurotransmitter involved in memory and attention in the brain.

Professor Clive Ballard, director of research for the Alzheimer's Society, which co-funded the new study, said around 50,000 people in the UK are currently thought to be on the drugs - just 10% of all people with Alzheimer's.

He said the research suggests hundreds of thousands could benefit overall, either by staying on the drugs into the later stages of the disease or being prescribed them in the first place.

He said: "This research - if acted upon - has the potential to change the lives of up to 450,000 more people today and many more in the future.

"It could mean many more people being able to stay on the drugs or accessing the drugs.

"It also adds vital weight to the argument that a diagnosis of dementia is essential.

"Only then can people be given the opportunity to try these drugs, which could bring real benefits into the later stages of the disease."

Only about 41% of people with dementia currently have a diagnosis.

The research, published in the New England Journal of Medicine, involved 295 patients with mild to moderate Alzheimer's disease who had been taking donepezil for at least three months, and were about to move towards the severe end of the disease.

They were split into four groups. The first continued taking donepezil, the second continued with donepezil and started taking memantine, while the third were taken off donepezil but started taking memantine. The fourth group were given two dummy drugs and acted as controls.

Over the course of a year, each person's mental abilities were tested through a range of questions, including recalling what time of year, season, date, day and month it was.

Patients were also asked to take part in language and writing tests.

Functioning ability was also measured, with scores given for how patients managed tasks such as eating, drinking, dressing, personal hygiene, brushing teeth, taking a bath or shower and using a toilet or commode.

The findings showed there was a statistically significant benefit from both drugs when it came to mental ability and functioning into the later stages of the disease.

Professor Robert Howard, lead author on the study, from the Institute of Psychiatry at King's College London, said donepezil in particular made a real difference to patients and their carers.

"When we talk about clinically significant benefits, we are talking about benefits that patients, their caregivers and doctors would actually notice," he said.

With donepezil, "it's as if the clock has been turned back four months" in terms of cognitive symptoms, and three months in terms of functioning, he said.

He added: "These treatments are symptomatic treatments, they don't actually slow down the rate of Alzheimer's disease - they are not a cure.

"But the improvements in symptoms they produce are important to patients, caregivers and those of us who look after the patients."

While combining the drugs did not seem to provide extra benefit, Prof Howard said he believed this was because the study was not large enough.

"It's fair to say both these drugs have independent positive good effects in patients at this stage of dementia," he added.

"Both these drugs have independent benefits but our trial was probably not large enough to be able to show superiority of the combination over donepezil alone.

"If you were to ask me what advice I would give to doctors and caregivers - and this is what I've told my colleagues - first of all there is robust evidence to support continuing donepezil, not stopping or restricting its use to mild to moderate stages as Nice (the National Institute for Health and Clinical Excellence) advises.

"It's probably worth carrying on for at least a year after patients leave the mild to moderate bracket.

"Secondly, both drugs - because they have independent effects in this group - I would advise my colleagues to... carry on with donepezil and add in memantine."

Prof Ballard said about a third of the 750,000 people in the UK with dementia are at an advanced stage of the disease.

He said Nice guidance does not stop doctors continuing patients on treatment as long as there is clinical benefit.

Prof Ballard described Alzheimer's as "a savage disease".

He continued: "Sadly what we do see is that when you stop these treatments, behavioural symptoms get worse."

Donepezil, which is commonly known by the brand name Aricept, is now available in generic form and costs around £11.97 per patient per month.

Memantine, which is approved by Nice for moderate to severe Alzheimer's, will become a cheaper generic drug once the patent for Ebixa expires.

As of March 2011, Nice listed the cost of the drug as £34.50 a month, but this is expected to fall once it comes off patent.

Memantine blocks NMDA glutamate receptors, which can play a key role in learning and memory.

Dr Simon Ridley, head of research at Alzheimer's Research UK, said: "Trials such as this are extremely important for informing decisions about the way medication is prescribed, potentially helping even more people."

A statement from Nice said: "Nice guidance on the use of donepezil and other acetylcholinesterase inhibitors does not include any specific recommendations on when to discontinue their use.

"Instead it says that treatment should only be continued while the drugs are 'considered to be having a worthwhile effect on cognitive, global, functional or behavioural symptoms'.

"So, if the drugs are still providing patients with benefit, then Nice guidance supports their continued use, subject to their licensed indications."

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