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4 March 2008 | Volume 148 Issue 5 | Pages 379-397
Background: The effectiveness of the 5 U.S. Food and Drug Administration–approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear.
Purpose: To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia.
Data Sources: Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006.
Study Selection: English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale.
Data Extraction: Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate.
Data Synthesis: 96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior.
Limitations: Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments.
Conclusions: Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.
Author and Article Information
From McMaster University, Hamilton, Ontario, Canada.
Disclaimer: The authors are solely responsible for the content of this review. The opinions expressed herein do not necessarily reflect the opinions of the Agency for Healthcare Research and Quality, the Ontario Ministry of Health and Long-Term Care, or the McMaster Evidence-based Practice Center.
Grant Support: Parminder Raina holds a Canadian Institute of Health Research Investigator award and an Ontario Premier's Research Excellence award. The original systematic review was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services (contract no. 290-02-0020). The update to this review was funded by the Ontario Ministry of Health and Long-Term Care and the McMaster University Evidence-based Practice Center.
Potential Financial Conflicts of Interest: Honoraria: P. Santaguida (American College of Physicians).
Requests for Single Reprints: Parminder Raina, PhD, McMaster University Evidence-based Practice Center, Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, DTC Room 306, Hamilton, Ontario L8S 4L8, Canada; e-mail, praina{at}mcmaster.ca.
Current Author Addresses: Drs. Raina, Santaguida, Ismaila, Patterson, Cowan, Levine, Booker, and Oremus: McMaster University Evidence-based Practice Center, Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main Street West, DTC Room 306, Hamilton, Ontario L8S 4L8, Canada. CLINICAL GUIDELINES
Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline
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