Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline.
BACKGROUND
The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear.


OBJECTIVE
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.


METHODS
Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006.


METHODS
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.


METHODS
Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate.


RESULTS
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.


CONCLUSIONS
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.
Raina
Parminder
P
McMaster University, Hamilton, Ontario, Canada. praina@mcmaster.ca
Santaguida
Pasqualina
P
Ismaila
Afisi
A
Patterson
Christopher
C
Cowan
David
D
Levine
Mitchell
M
Booker
Lynda
L
Oremus
Mark
M
D000203:Activities of Daily Living; D000339:Affect; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition; D003704:Dementia / Q000188:drug therapy* / Q000523:psychology; D000077265:Donepezil; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005702:Galantamine / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008559:Memantine / Q000627:therapeutic use*; D048448:Phenylcarbamates / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011788:Quality of Life; D000068836:Rivastigmine; D013619:Tacrine / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D013619:Tacrine; D000077265:Donepezil; D000068836:Rivastigmine; D008559:Memantine