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Randomised controlled trial
Cessation of donepezil is associated with clinical decline in patients with moderate-to-severe Alzheimer's disease compared to continuation of donepezil or addition or substitution of memantine
  1. Pierre N Tariot
  1. Banner Alzheimer's Institute, Phoenix, Arizona, USA
  1. Correspondence to: Pierre N Tariot
    Banner Alzheimer's Institute, 901 E Willetta ST, Phoenix, Arizona 85006, USA; Pierre.tariot{at}

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More than half of persons with Alzheimer's disease are at moderate or severe stages, and evidence defining best practice for them is limited. Previous clinical trials in these patients, as summarised by Howard et al,1–5 have shown that treatment with donepezil or memantine only, or the addition of memantine to donepezil, confers benefit in cognition and daily function. Building upon these, Howard and colleagues aimed to address the relative benefit of continuing donepezil, adding or substituting memantine, or stopping donepezil in these patients.


This was a 52-week multicentre, allocation concealed, randomised, double-blind, placebo-controlled clinical trial in persons with moderate to severe Alzheimer's dementia receiving stable doses of donepezil. Participants were randomised to treatment with ongoing donepezil, ongoing donepezil plus memantine, memantine only or …

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  • Competing interests PNT has received consulting fees and stock options from Adamas. His institution receives research support from Pfizer and Janssen.