Donepezil and rivastigmine in the treatment of Alzheimer's disease: a best-evidence synthesis of the published data on their efficacy and cost-effectiveness.
BACKGROUND
Various drugs have been approved for the treatment of Alzheimer's disease (AD) in the United States and Canada, including donepezil and rivastigmine, although questions remain as to their efficacy, effectiveness, and long-term benefits.


OBJECTIVE
The goal of this study was to conduct a best-evidence synthesis of data on the efficacy and cost-effectiveness of donepezil and rivastigmine in the treatment of AD.


METHODS
Relevant published randomized controlled trials (RCTs) and Phase IV open-label extension studies (excluding abstracts) were identified through searches of MEDLINE, HealthSTAR, and PsycINFO for the period January 1984 to October 2001. The bibliographies of retrieved articles were searched for additional publications. For inclusion in the best-evidence synthesis, clinical trials had to pass a blinded quality assessment (score > or =5 on the Jadad scale) and use National Institute of Neurological and Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria. Economic studies were selected using National Health Service Centre for Reviews and Dissemination criteria for reporting critical summaries of economic evaluations.


RESULTS
Nine RCTs of donepezil and 2 of rivastigmine were identified and met inclusion criteria for the best-evidence synthesis. Eight donepezil trials and both rivastigmine trials included patients with mild AD (Mini-Mental State Examination [MMSE] score, 15-27) or moderate AD (MMSE score, 8-14); 1 donepezil trial included patients with moderate or severe AD (MMSE score, 0-7). In the RCTs of donepezil, the mean decrease in scores on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) was greater with active treatment than with placebo (lower scores indicate less cognitive deterioration). In the RCTs of rivastigmine, ADAS-cog scores decreased over the follow-up period with both active treatment and placebo; however, scores decreased more with active treatment. Three Phase IV studies of donepezil and I Phase IV study of rivastigmine were identified. Their results were consistent with those of the RCTs. Ten economic studies (7 donepezil, 3 rivastigmine) were identified and reviewed. In 4 of the donepezil studies and all 3 rivastigmine studies, use of the drug cost less than a no-drug strategy.


CONCLUSIONS
The efficacy data indicate that both donepezil and rivastigmine can delay cognitive impairment and deterioration in global health for at least 6 months in patients with mild to moderate AD. Patients receiving active treatment will have more favorable ADAS-cog scores for at least 6 months, after which their scores will begin to converge with those of patients receiving placebo. Differences in methodology, types of direct or indirect costs included, and sources of cost data made it difficult to compare and synthesize findings of the economic studies; therefore, the cost-effectiveness data are inconclusive.
Wolfson
Christina
C
Centre for Clinical Epidemiology and Community Studies, S.M.B.D. Jewish General Hospital, Montreal, Quebec, Canada. tinaw@epid.jgh.mcgill.ca
Oremus
Mark
M
Shukla
Vijay
V
Momoli
Franco
F
Demers
Louise
L
Perrault
Anne
A
Moride
Yola
Y
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000453:epidemiology; D002170:Canada / Q000453:epidemiology; D002219:Carbamates / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D048448:Phenylcarbamates; D010880:Piperidines / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000068836:Rivastigmine; D016896:Treatment Outcome
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D000077265:Donepezil; D000068836:Rivastigmine