The benefits and risks associated with cholinesterase inhibitor therapy in Alzheimer's disease.
The 'second-generation' cholinesterase inhibitors (ChEIs), donepezil, galantamine and rivastigmine, are a class of medications that are currently approved for the treatment of mild-to-moderate Alzheimer's disease (AD). These medications have proven efficacy in improving cognition, behaviour, activities of daily living, and global functioning in mild-to-moderate AD. They have also been shown to reduce caregiver stress and to delay time to nursing home placement. Two separate meta-analyses have indicated that ChEIs confer a modest but significant therapeutic benefit in the treatment of AD, despite higher rates of treatment discontinuation and side effects than placebo. There is growing evidence to support their efficacy in treating moderate-to-severe AD. ChEIs are generally well-tolerated, with side effects that tend to be dose-related and are most problematic during dose titration. The most common adverse effects, related to cholinergic stimulation in the brain and peripheral tissues, include gastrointestinal, cardiorespiratory, extrapyramidal, genitourinary, and musculoskeletal symptoms, as well as sleep disturbances. Few clinically significant drug-drug interactions with ChEIs have been identified. Three head-to-head trials of ChEIs in the treatment of AD have been published to date, but are limited due to their open-label design, rates of titration, and the drug dosage levels utilised. Further study is needed to examine other indications for ChEIs, as well as their combination with newer treatments, such as memantine.
Thompson
Sarah
S
Sunnybrook and Women's College Health Sciences Centre, Department of Psychiatry, Rm FG-05, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada.
Lanctôt
Krista L
KL
Herrmann
Nathan
N
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001919:Bradycardia / Q000139:chemically induced; D002493:Central Nervous System Diseases / Q000139:chemically induced; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015897:Comorbidity; D000077265:Donepezil; D004311:Double-Blind Method; D004341:Drug Evaluation; D004347:Drug Interactions; D005260:Female; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use; D007326:Institutionalization; D008137:Longitudinal Studies; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use; D015201:Meta-Analysis as Topic; D051379:Mice; D008875:Middle Aged; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D048448:Phenylcarbamates / Q000009:adverse effects / Q000627:therapeutic use; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068836:Rivastigmine; D016037:Single-Blind Method; D012893:Sleep Wake Disorders / Q000139:chemically induced; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine; D008559:Memantine