Discontinuing donepezil in Alzheimer’s patients as their disease worsens could double the risk of admission into a nursing home within a year, suggests a study published in The Lancet Neurology on 26 October 2015
Donepezil, a cholinesterase inhibitor, licensed for the symptomatic treatment of mild-to-moderate Alzheimer’s disease, is usually withdrawn once a patient’s cognitive symptoms become more severe because of a lack of perceived benefit and to save on costs.
However, a study by researchers at University College London (UCL) suggests that the drug should not be withdrawn so quickly.
The study included 295 patients with moderate-to-severe Alzheimer’s disease who had taken donepezil continuously for at least three months at a dose of 10mg for the previous six weeks. The patients were randomised to continue taking donepezil 10mg per day alone, discontinue donepezil, discontinue donepezil and start memantine 20mg per day, or continue donepezil 10mg per day and start memantine 20mg per day. Patients recruited to the study had a score of between 5 and 13 on the Standardised Mini-Mental State Examination.
During the first year, fewer patients in both groups that continued taking donepezil entered a nursing home, compared with patients who stopped taking the drug (hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.29–3.39).
After a year, the decision to continue treatment further was left to the doctor and patient; this limited the patient data available, and the analysis showed that donepezil did not reduce the likelihood of admittance to a nursing home in the following three years (HR 0.89, CI 0.58–1.35). Memantine, an NMDA receptor antagonist licensed for moderate to severe Alzheimer’s disease, was found to have no impact on nursing home admittance at any stage.
“We are not saying that the treatment is actually slowing down Alzheimer’s disease,” said Robert Howard, study lead and professor of old age psychiatry at UCL, at a press conference on 26 October 2015. “The treatment is continuing to improve symptoms in a way that helps patients to maintain independence and it is doing it for longer and later into the illness.”
Howard said the delay to nursing home admission was mediated through preserved participation in activities of daily living, such as feeding and dressing.
“If you look at the factors that predict why people go into a care home, it is more likely to be that they have lost those functions rather than because their memory has got worse. We showed in the initial trial that there was a significant difference in the preservation of those functions
,” he said.
The brains of patients with Alzheimer’s disease have low levels of the neurotransmitter acetylcholine. Cholineserase inhibitors, such as donepezil, work by blocking the enzyme acetylcholinesterase from breaking down acetylcholine, thereby helping to prolong the neurotransmitter’s effect.
Commenting on the study, Ian Maidment, senior lecturer in clinical pharmacy at Aston University and spokesperson for the Royal Pharmaceutical Society, says: “Most people with dementia and their carers want to live at home for as long as possible. Stopping donepezil could worsen the ability of the person with dementia to cope with the usual activities of daily living, which may mean that living at home becomes impossible.
“Therefore, you should certainly think twice about withdrawing donepezil if you have a friend or relative who is on donepezil and ‘just about’ managing at home with appropriate support from carers,” he adds.
Frank Gray, physician lead, Rare Disease Unit at GlaxoSmithKline Medicines Research Centre, says: “Currently when a patient’s Alzheimer’s disease gets worse their medication is stopped to save on costs as it is felt they no longer get benefit. This study shows that may not be the best option.”
Donepezil is now generic “so additional cost to healthcare system would be limited if medication was continued”, Gray adds. Generic donepezil costs from £21.59 per year (based on the drug tariff, which lists reimbursement prices for pharmacy contractors), whereas the average cost of residential care for people with dementia is estimated at between £30,732 and £34,424, according to the Alzheimer’s Society, who funded the study along with the Medical Research Council.
 Howard R, McShane R, Lindesay J et al. Nursing home placement in the donepezil and memantine in moderate to severe Alzheimer’s disease (DOMINO-AD) trial: secondary and post-hoc analyses. The Lancet Neurology 2015. doi:10.1016/S1474-4422(15)00258-6