Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer's disease: systematic review of the 'real-world' evidence.
OBJECTIVE
The purpose of this systematic review was to compare the safety and tolerability of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine for treating mild to moderate Alzheimer's disease (AD) patients in routine clinical practice.


METHODS
Electronic databases (Cochrane Library, Medline, EMBASE; accessed October 2008) and manual bibliographic searches were conducted to identify head-to-head non-randomised studies examining ChEIs for the treatment of AD. Data were extracted by 2 independent reviewers.


RESULTS
Twelve head-to-head studies comparing ChEIs met the pre-specified inclusion criteria; 6 retrospective analyses and 6 prospective cohort studies. Donepezil was the most widely studied treatment and galantamine the least widely prescribed therapy. Fewer donepezil-treated subjects withdrew due to adverse events (AEs) compared with rivastigmine and galantamine-treated subjects. The incidence of gastrointestinal (GI) AEs was lower following treatment with donepezil compared with rivastigmine and galantamine. Non-GI (CNS and cardiovascular) AEs occurred at a low frequency, and had a similar incidence in subjects treated with the different ChEIs.


CONCLUSIONS
Subjects with mild to moderate AD treated in routine clinical practice with donepezil were more adherent to pharmacotherapy, and had a lower risk of GI AEs compared with rivastigmine or galantamine. This finding accords with results reported in the randomised clinical trial literature.
Lockhart
I A
IA
Pfizer Ltd., Walton-On-The-Hill, Surrey KT20 7NS, UK. Ian.Lockhart @ pfizer.com
Mitchell
S A
SA
Kelly
S
S
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000077265:Donepezil; D019317:Evidence-Based Medicine; D005702:Galantamine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000009:adverse effects; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D000068836:Rivastigmine
D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine