The drug, donepezil, is reported to cost 6p for a daily course

Donepezil is usually withdrawn as a treatment for people with moderate to severe Alzheimer’s disease as it had been thought to provide little benefit.

In this study, researchers wanted to see if this was a hasty decision and people should actually continue to take the drug – they carried out a randomised controlled study to look at the issue.

People with moderate to severe Alzheimer’s, who were living in the community, were randomly allocated to discontinue or continue taking donepezil, either alone or in combination with another Alzheimer’s drug called memantine, or switching to memantine alone.

The main outcome the researchers looked at was whether these people ended up being placed in a nursing home. The results showed discontinuing donepezil roughly doubled the chance of nursing home placements during the first year. There was no significant difference between these groups in the following three years.

This study cannot prove donepezil was directly responsible for keeping people from being admitted to nursing homes. It examined the effects of continued donepezil treatment on nursing home placement – not on cognitive function. But the researchers did speculate donepezil could help people with Alzheimer’s cope better with day-to-day tasks, such as dressing.

Guidelines for the best practice for treating Alzheimer’s continue to evolve, so it is likely these results will feed into that process. 

Where did the story come from?

The study was carried out by researchers from various different UK institutions, including University College London, King’s College London, Oxford Health NHS Foundation Trust, the University of Leicester, the University of Edinburgh, Five Boroughs Partnership NHS Foundation Trust, the Centre for Ageing and Vitality (Newcastle upon Tyne), the University of Manchester, the University of Nottingham, and the University of Southampton.

It was funded by the Medical Research Council and the UK Alzheimer’s Society, and was published in the peer-reviewed The Lancet Neurology.

The researchers declared that all the drugs and placebo were provided by Pfizer-Eisai and Lundbeck, but the pharmaceutical companies had no involvement in the design or conduct of the study, or the analysis or reporting of the data.

The researchers also declared they received payments from various different major pharmaceutical companies that specialise in drugs related to central nervous system diseases for work unrelated to this study.

The UK media’s reporting of this study was accurate and balanced. The Daily Telegraph reported that although the drug was originally licensed for only mild and moderate dementia, based on the results of a trial in 2012, the National Institute for Health and Care Excellence (NICE) told doctors they are free to continue prescribing donepezil in the later stages of the disease. But many GPs stop prescribing the medication because of its side effects, which include nausea and an irregular heartbeat.

Many news sources discuss the potential economic implications of the study, pointing out that a year’s worth of donepezil costs around ¬£21 a year, compared with a year’s worth of care home costs – estimated to be between ¬£30,732 and ¬£34,424 a year. If the results of the study were replicated at a population level, this could save the NHS a considerable sum of money. 

What kind of research was this?

This randomised, double-blind, placebo-controlled study assessed the impact of continuing or discontinuing the Alzheimer’s drug donepezil on nursing home placement in people with moderate to severe Alzheimer’s disease.

Alzheimer’s disease is the most common cause of dementia. The word dementia describes a set of symptoms that can include memory loss and difficulties with thinking, problem solving or language. According to the Alzheimer’s Society, there are more than 520,000 people with Alzheimer’s disease in the UK.  

Donepezil, commonly sold under the brand name Aricept, is a drug licensed to treat mild to moderate Alzheimer’s disease, along with the alternative drugs galantamine and rivastigmine. It’s recommended that cognitive function is assessed after three months to give an indication of how well the drug is working.

Another drug called memantine has a slightly different mechanism of action and is licensed for the treatment of moderate to severe Alzheimer’s. The researchers looked at discontinuing or continuing donepezil, either alone or in combination with memantine, or switching to memantine alone. 

What did the research involve?

This study included a total of 295 individuals (average age 77 years) living in the community in England and Scotland between 2008 and 2010, and who were receiving specialist care for their Alzheimer’s.

People were included in the study if they had moderate or severe Alzheimer’s disease and had been prescribed donepezil continuously for at least three months at a dose of 10mg for at least the previous six weeks.

All participants in the study had a score of between 5 and 13 on the Mini-Mental State Examination (MMSE). This is a standardised screening test used to evaluate cognitive impairment in older adults.

Individuals were excluded if they had severe or unstable medical disorders, were receiving memantine, or had been deemed unlikely to adhere to the study regimens.

They were assigned to one of four treatment groups for one year:

• group one – continue donepezil
• group two – discontinue donepezil
• group three – discontinue donepezil and start taking memantine
• group four – continue donepezil and start taking memantine

All people took two drugs each day, combining a placebo for the respective drug when it wasn’t given so participants and assessors were unaware of which group they had been allocated to – for example, donepezil with memantine placebo. 

Place of residence was recorded during the first year of the trial and then every six months for the next three years. 

What were the basic results?

Out of the total of 295 study participants, 162 (55%) were admitted to a nursing home within four years of the start of the trial.

In brief, the researchers found the groups who discontinued donepezil had a roughly doubled chance of nursing home placement during the first year, compared with those who continued taking the drug (hazard ratio [HR] 2.09, confidence interval [CI] 1.29 to 3.39).

There was, however, no difference in risk of nursing home placement for any of the four groups during the following three years. Starting memantine – either alone or in combination – was found to have no effect on risk of nursing home placement.  

How did the researchers interpret the results?

The researchers concluded by saying that, “Withdrawal of donepezil in patients with moderate to severe Alzheimer’s disease increased the risk of nursing home placement during 12 months of treatment, but made no difference during the following three years of follow-up.

“Decisions to stop or continue donepezil treatment should be informed by potential risks of withdrawal, even if the perceived benefits of continued treatment are not clear.” 

Conclusion

This randomised controlled trial assessed the impact of continuing or discontinuing the Alzheimer’s drug donepezil on the chances of nursing home admission in people with moderate to severe Alzheimer’s.

The study examined discontinuing or continuing donepezil, either alone or in combination with memantine, or switching to memantine alone. Memantine is currently licensed for the treatment of moderate to severe Alzheimer’s, while donepezil is only licensed for mild to moderate forms of the disease.

In this trial, people had already been taking donepezil for three to six months or more. These drugs are only given by specialists, and the continuation or discontinuation of the drug is usually decided on an individual basis, depending on a person’s response and its effects on cognitive function. 

The results of this study showed discontinuing donepezil was associated with an increased chance of participants being placed in a nursing home in the first year of not taking the drug, compared with those who continued to take it.

Meanwhile, starting memantine had no effect. There was, however, no significant difference between these groups in the three years after the drugs had been stopped.

Although randomised controlled trials are the best study design to look at whether a treatment works or not, it is difficult to draw firm conclusions from the results of this study alone.

The study has primarily examined the effects of continued donepezil treatment on whether someone is placed in a nursing home, not on cognitive function. We do not know donepezil reduced Alzheimer’s symptoms and this was directly responsible for helping the person remain independent in their own home.

The researchers also have not measured any side effects in individuals who continued to take this drug, so we can’t assess the impact on their quality of life.

It could be the case that some people would actually be happier in a nursing home. It would be presumptuous to assume going into a nursing home automatically represented a failure in treatment.

Although there are currently no drugs that can cure Alzheimer’s disease, research like this is important as it could prove the benefits of early treatment, which may reduce the severity of symptoms and slow the progression of the disease.

If you or anyone you know has experienced the following symptoms on more than a few occasions, it is important to seek medical help:

• forgetting recent conversations or events
• forgetting the names of places and objects
• repeating yourself regularly, such as asking the same question several times
• showing poor judgement or finding it harder to make decisions
• becoming unwilling to try out new things or adapt to change

Read more about the possible early warning signs of Alzheimer’s disease and other dementia-related conditions.