Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials.

TY - JOUR

T1 - Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials.

AU - Kaduszkiewicz, Hanna

AU - Zimmermann, Thomas

AU - Beck-Bornholdt, Hans-Peter

AU - van den Bussche, Hendrik

PY - 2005

Y1 - 2005

N2 - OBJECTIVES: Pharmacological treatment of Alzheimer's disease focuses on correcting the cholinergic deficiency in the central nervous system with cholinesterase inhibitors. Three cholinesterase inhibitors are currently recommended: donepezil, rivastigmine, and galantamine. This review assessed the scientific evidence for the recommendation of these agents. DATA SOURCES: The terms "donepezil", "rivastigmine", and "galantamine", limited by "randomized-controlled-trials" were searched in Medline (1989-November 2004), Embase (1989-November 2004), and the Cochrane Database of Systematic Reviews without restriction for language. STUDY SELECTION: All published, double blind, randomised controlled trials examining efficacy on the basis of clinical outcomes, in which treatment with donepezil, rivastigmine, or galantamine was compared with placebo in patients with Alzheimer's disease, were included. Each study was assessed independently, following a predefined checklist of criteria of methodological quality. RESULTS: 22 trials met the inclusion criteria. Follow-up ranged from six weeks to three years. 12 of 14 studies measuring the cognitive outcome by means of the 70 point Alzheimer's disease assessment scale--cognitive subscale showed differences ranging from 1.5 points to 3.9 points in favour of the respective cholinesterase inhibitors. Benefits were also reported from all 12 trials that used the clinician's interview based impression of change scale with input from caregivers. Methodological assessment of all studies found considerable flaws--for example, multiple testing without correction for multiplicity or exclusion of patients after randomisation. CONCLUSION: Because of flawed methods and small clinical benefits, the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer's disease is questionable.

AB - OBJECTIVES: Pharmacological treatment of Alzheimer's disease focuses on correcting the cholinergic deficiency in the central nervous system with cholinesterase inhibitors. Three cholinesterase inhibitors are currently recommended: donepezil, rivastigmine, and galantamine. This review assessed the scientific evidence for the recommendation of these agents. DATA SOURCES: The terms "donepezil", "rivastigmine", and "galantamine", limited by "randomized-controlled-trials" were searched in Medline (1989-November 2004), Embase (1989-November 2004), and the Cochrane Database of Systematic Reviews without restriction for language. STUDY SELECTION: All published, double blind, randomised controlled trials examining efficacy on the basis of clinical outcomes, in which treatment with donepezil, rivastigmine, or galantamine was compared with placebo in patients with Alzheimer's disease, were included. Each study was assessed independently, following a predefined checklist of criteria of methodological quality. RESULTS: 22 trials met the inclusion criteria. Follow-up ranged from six weeks to three years. 12 of 14 studies measuring the cognitive outcome by means of the 70 point Alzheimer's disease assessment scale--cognitive subscale showed differences ranging from 1.5 points to 3.9 points in favour of the respective cholinesterase inhibitors. Benefits were also reported from all 12 trials that used the clinician's interview based impression of change scale with input from caregivers. Methodological assessment of all studies found considerable flaws--for example, multiple testing without correction for multiplicity or exclusion of patients after randomisation. CONCLUSION: Because of flawed methods and small clinical benefits, the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer's disease is questionable.

M3 - SCORING: Zeitschriftenaufsatz

VL - 331

SP - 321

EP - 327

JO - BMJ-BRIT MED J

JF - BMJ-BRIT MED J

SN - 0959-535X

IS - 7512

M1 - 7512

ER -