Care and cure magazine - Winter 2015
Although there are many promising drugs for dementia in development, it is important to make the most of the drugs that are already available. The DOMINO-AD trial has shown that one drug currently in use could be helpful for people in the later stages of Alzheimer's disease.
When new drugs are being tested in people they progress through different stages of clinical trials. Phase one focuses on the safety of the drug, which is often tested in a few healthy young people. If that is successful, it progresses to phase two where the drug is tested for biological effects in a few dozen patients. The final stage, phase three, is the definitive trial to test the drug in hundreds of patients to see if it has an effect on the disease.
New drugs have to overcome all these hurdles before they can be approved and prescribed by doctors. However a lesser-known stage, phase four, examines the effectiveness of the drug once it is already being widely prescribed. This phase can help to identify any additional side-effects or groups of people who might benefit from receiving the drug.
Acetylcholinesterase inhibitors, the most popular class of dementia drugs which includes donepezil (Aricept), are only recommended for people with mild-to-moderateAlzheimer’s disease. The DOMINO-AD trial was set up in 2008 to find out whether these drugs could benefit people in the later stages of the condition. It studied the effects of withdrawing or continuing donepezil treatment in nearly 300 people with moderate-to-severe Alzheimer's disease.
The trial, which was funded by the Medical Research Council and Alzheimer's Society, found that people who continued taking donepezil showed a third less decline in their memory, compared to those who were given a placebo. It also had benefits for people's functional abilities such as dressing or eating.
'Even when patients had progressed to the moderate or severe stages of their dementia, continuing with donepezil treatment provided modest benefits in cognitive function and in how well people could perform their daily activities,' says Robert Howard, Professor of Old Age Psychiatry at University College London, who led the trial.
These results, published in 2012, were contrary to the perceptions of many doctors at the time. A year later, two-thirds of old age psychiatrists surveyed felt that the future practice of prescribing donepezil and similar drugs would be altered based on the trial's results.
'With no new treatments for Alzheimer's disease in over a decade, it is absolutely crucial that we make the most of the drugs we have available,' says Dr Doug Brown, Director of Research and Development at Alzheimer's Society.
A follow-up of the people who took part in the study, published in October, found that continuing to take donepezil also reduced their chances of moving to a nursing home. This benefit did not last beyond the end of the trial when the participants were able to choose their medication with their doctor.
Professor Howard says, 'Our new results show that these benefits translate into a delay in becoming dependent on residential care, a point that many of us dread. We are all impatient for the advent of true disease-modifying drugs that can slow or halt the Alzheimer process, but donepezil is available right now and at modest cost.'