title: The clinical benefits of rivastigmine may reflect its dual inhibitory mode of action: an hypothesis.
abstract: Recent health technology assessments have given us the go-ahead to use cholinesterase inhibitors, which, in combination with community services, are currently the most appropriate treatment for patients with Alzheimer's disease (AD). Initial research focused upon acetylcholinesterase (AChE)-selective agents, but it is now thought that dual inhibitors of AChE and butyrylcholinesterase (BuChE) may provide more sustained efficacy over the course of AD and may help to slow disease progression. Rivastigmine is a potent inhibitor of AChE and BuChE and has demonstrated broad benefits across the severity of AD and across the cognitive, functional and behavioural domains of AD. In addition, rivastigmine has shown cognitive and behavioural benefits in patients with dementia with the Lewy body variant of AD. These benefits may reflect the inhibition of both AChE and BuChE, as demonstrated by significant correlations between cognitive improvements and cholinesterase inhibition in rivastigmine-treated patients with AD. Rivastigmine shows a clear dose-response relationship, and physicians should aim to maintain patients on doses of 6 mg/day or higher, to a maximum of 12 mg/day. As with all cholinesterase inhibitors, rapid forced dose escalation may increase the incidence of typical cholinergic side-effects, resulting in lower maintenance doses. In a chronic disease such as AD, there is time to implement slow dose escalation and higher final maintenance doses. If used appropriately, the benefits of rivastigmine seen in clinical practice may prove to be even greater than those reported in clinical trials.
authors.affiliation: Department of Old Age Psychiatry, Kingshill Research Centre, Victoria Hospital, Swindon, Wilts, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bullock
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D002091:Butyrylcholinesterase; D002219:Carbamates / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003704:Dementia / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D048448:Phenylcarbamates; D000068836:Rivastigmine
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D002091:Butyrylcholinesterase; D000068836:Rivastigmine