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Donepezil outperforms other cognitive enhancers in patients with Alzheimer’s dementia

Sharon E. Straus

Donepezil was most effective at improving cognition in patients with Alzheimer’s dementia when compared with rivastigmine, galantamine, memantine and placebo, according to a systematic review and network meta-analysis published in the Journal of the American Geriatrics Society.

“Alzheimer’s dementia is a global concern that has a substantial impact on patients, caregivers and health care systems,” Sharon E. Straus, MD, of the Li Ka Shing Knowledge Institute at Saint Michael’s Hospital in Toronto, told Healio Family Medicine. “It is critical that we understand the comparative safety and effectiveness of these medications to guide appropriate decision making among patients and their caregivers.”

According to researchers, previous systematic reviews of cognitive enhancers only examined randomized control trial data, restricting the applicability of the findings to daily practice.

Straus and colleagues analyzed 142 studies containing 33,889 patients for their review. According to Straus, their review contained 111 studies and more than 22,000 patients who had not been part of any previous review.

Studies included in the review provided behavior and cognitive outcomes using one of several Alzheimer’s related assessment tests. Information on mortality and serious adverse events, particularly those leading to bradycardia, disability, diarrhea, falls, headache, life-threatening or fatal hospitalization and nausea were also reported. All medications were compared with placebo.

The researchers found that donepezil was most likely to be effective at improving cognition on the Alzheimer’s Disease Assessment Scale cognition subscale (mean difference, –3.29; 95% Credible Interval, -4.57 to –1.99), according to the surface under the cumulative ranking curve. Galantamine also improved cognition compared with placebo on the Alzheimer’s Disease Assessment Scale cognition subscale. On the Mini-Mental State Examination, donepezil, transdermal rivastigmine, and donepezil plus memantine improved cognition vs. placebo.

The findings also suggested that donepezil plus memantine improved behavior on the Neuropsychiatric Inventory vs. placebo, and that galantamine decreased odds of mortality. In addition, when compared with placebo, oral rivastigmine increased risk for headache, diarrhea, nausea and vomiting; donepezil increased risk for diarrhea, nausea and vomiting; and galantamine increased risk for vomiting. No medication studied increased the risk for bradycardia, falls or serious adverse events.

“It is critical that physicians discuss the risks and benefits of these medications,” Straus said. “If the patient decides to use the medication, physicians should start with a low dose and monitor the patient closely for adverse events.” - by Janel Miller

Disclosures: The authors report no relevant financial disclosures.