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EFFECTIVENESS OF ACETYLCHOLINESTERASE INHIBITORS AND MEMANTINE IN THE TREATMENT OF ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW AND COMPARATIVE ANALYSIS

R. Modha, G. Pietri, B. Schauble, M. Gaudig

J Aging Res Clin Practice 2013;2(1):17-31

Introduction: Many randomized throughout placebo-controlled trials have investigated the use of acetylcholinesterase inhibitors (AChEIs) and memantine in Alzheimer’s disease (AD). However, few trials comparing different drugs have been conducted, meaning their relative effectiveness is not well-established. Methods: A systematic review of randomized controlled trials was conducted to identify the evidence base for donepezil, galantamine, rivastigmine, and memantine when used within European licensing limits. Literature databases (start to March 2010) and conference proceedings (2007 - 2010) were screened. Mixed treatment comparisons (MTC), were used to evaluate the comparative efficacy and safety. Results: Fifty-eight studies were identified; 48 were placebo comparisons, indicating the limited comparative evidence. Direct meta-analysis demonstrated that AChEIs are associated with significant advantage over placebo in cognitive outcomes at 3 months and 6 months (p<0.05); the pooled results of two studies did not indicate a significant advantage for memantine over placebo. An advantage for galantamine and donepezil over placebo in behavior at 6 months (NPI scale) was observed. MTC analysis identified no significant difference between AChEIs for cognition at 3 and 6 months, nor for behavior. A small increase in frequency of any adverse event was observed for AChEIs (approximate relative risk of 1.1) but not for memantine. Oral rivastigmine was associated with a higher risk of all and specific adverse events than other treatments. Conclusions: The benefits of AChEIs but not memantine on cognition in AD were established. No clear difference in cognition or behavior is apparent between AChEIs.

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