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| |  AGS: Donepezil Better Tolerated Than Rivastigmine, Efficacy Comparable By W. A. Thomasson, PhD Special to DG News CHICAGO, IL -- May 11, 2001 -- Results of the first head-to-head comparison of the cholinesterase inhibitors, donepezil and rivastigmine, show both drugs to provide effective cognitive improvement in patients with Alzheimer’s dementia, but donepezil to have fewer cholinergic side effects. Results were reported yesterday at the annual meeting of the American Geriatrics Society by R. Bullock, MD, of Buckhill Research Centre in Swindon (UK) and his colleagues at universities in Northern Ireland, South Africa, and Switzerland. The study included 111 patients with mild to moderate Alzheimer’s disease who had not previously been treated with either drug. Patients were titrated to the highest recommended dose of the study drug, if tolerated, or to the highest tolerated dose. Assignment to treatment was random, and cognitive raters (who used the cognitive subscale of the Alzheimer’s Disease Assessment Scale) were blind as to assigned medication, but the study was otherwise open-label. Results showed that 87.5 percent of the donepezil group was able to tolerate the highest recommended dose, compared to 47.3 percent of the rivastigmine-treated group. Nevertheless, cognitive assessment of patients at the dose actually reached showed no difference in efficacy at either four-week or 12-week time points. Treatment-related adverse events were more common in the rivastigmine group, being seen in 58.2 percent of patients compared to 42.9 percent of patients in the donepezil group. Most of the adverse events in both groups were mild to moderate and most commonly gastrointestinal; nevertheless, almost four times as many patients on rivastigmine as on donepezil (41.8 percent versus 10.7 percent) developed nausea and more than three times as many vomited (23.6 percent versus 7.1 percent). The frequency of serious or severe adverse events was below 10 percent and comparable in the two groups. Other aspects of the study found greater physician and caregiver satisfaction with donepezil, primarily on the basis of dosing frequency (q.d. versus b.i.d.) and titration schedule. As Dr. Bullock noted, these are averages across patients as a group. Individual patients may vary in their ability to tolerate different drugs. This led him to comment, "What people haven’t been doing until now is switching between [the various cognitive enhancers] if one doesn’t work. But I think that will start to happen more," now that a third such drug (galantamine) is available in the US. He added that in another study from his group, "We took people who didn’t manage to get a good result with [donepezil] and switched them to rivastigmine, and about half got an improvement. So people should be encouraged to switch like we do in any other branch of medicine."
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