Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study
Open accessAbstract
Background Dementia with Lewy bodies is a common form of dementia in the elderly, characterised clinically by fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism, and other neuropsychiatric features. Neuroleptic medication can provoke severe sensitivity reactions in patients with dementia of this type. Many deficits in cholinergic neurotransmission are seen in the brain of patients with Lewy-body dementia; therefore, drugs enhancing central cholinergic function represent a rationally-based therapeutic approach to this disorder. Rivastigmine, a cholinesterase inhibitor, was tested in a group of clinically characterised patients with Lewy-body dementia. Methods A placebo-controlled, double-blind, multicentre study was done in 120 patients with Lewy-body dementia from the UK, Spain, and Italy. Individuals were given up to 12 mg rivastigmine daily or placebo for 20 weeks, followed by 3 weeks rest. Assessment by means of the neuropsychiatric inventory was made at baseline, and again at weeks 12, 20, and 23. A computerised cognitive assessment system and neuropsychological tests were also used, and patients underwent close medical and laboratory safety analysis. Findings Patients taking rivastigmine were significantly less apathetic and anxious, and had fewer delusions and hallucinations while on treatment than controls. Almost twice as many patients on rivastigmine (37, 63%), than on placebo (18, 30%), showed at least a 30% improvement from baseline. In the computerised cognitive assessment system and the neuropsychological tests, patients were significantly faster and better than those on placebo, particularly on tasks with a substantial attentional component. Both predefined primary efficacy measures differed significantly between rivastigmine and placebo. After drug discontinuation differences between rivastigmine and placebo tended to disappear. Known adverse events of cholinesterase inhibitors (nausea, vomiting, anorexia) were seen more frequently with rivastigmine than with placebo, but safety and tolerability of the drug in these mostly multimorbid patients were judged acceptable. Interpretation Rivastigmine 6-12 mg daily produces statistically and clinically significant behavioural effects in patients with Lewy-body dementia, and seems safe and well tolerated if titrated individually.
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An RCT found no difference between rivastigmine and placebo on overall NPI scores or on a "Lewy body cluster" of symptoms (delusions, hallucinations, apathy, and depression) in Lewy body dementia.
“However, an RCT found no difference between rivastigmine and placebo on overall NPI scores or on a “Lewy body cluster” of symptoms (delusions, hallucinations, apathy, and depression).148”
From Assessment and management of behavioral and psychological symptoms of dementia (2015) · cites this paper as [148]
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- Authors
- McKeith, I., Del Ser, T., Spano, P., Emre, M., Wesnes, K., Anand, R., Cicin-Sain, A., Ferrara, R., & Spiegel, R.
- Affiliations
- Newcastle University (GB)
- University of Brescia (IT)
- Istanbul University (TR)
- Novartis (United States) (US)
- Novartis (Switzerland) (CH)
- Novartis (Italy) (IT)
- Corresponding author
- McKeith, Ian
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 356
- Issue
- 9247
- Pages
- 2031-2036
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2116249921
- Cited by
- 1,182
- References
- 3
- Citations by year
- 2026: 15 · 2025: 25 · 2024: 18 · 2023: 18 · 2022: 48 · 2021: 25 · 2020: 26 · 2019: 29 · 2018: 68 · 2017: 32 · 2016: 35 · 2015: 43 · 2014: 43 · 2013: 40 · 2012: 41
- FWCI
- 42.23
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- rivastigmine, dementia with Lewy bodies, cholinesterase inhibitors, cholinergic dysfunction, neuropsychiatric symptoms, delusions and hallucinations, apathy, anxiety, cognitive impairment, drug safety and tolerability, attention deficits
- MeSH terms
- Rivastigmine, Aged, Carbamates, Cholinesterase Inhibitors, Double-Blind Method, Female, Humans, Male, Middle Aged, Treatment Outcome, Lewy Body Disease, Phenylcarbamates
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