Skip to main content
    • Aa
    • Aa

Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer's disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine

  • Joanne Rodda (a1), Shirlony Morgan (a1) and Zuzana Walker (a1)

Background: The study aim was to conduct a systematic review of the evidence from randomized, placebo controlled trials related to the efficacy of donepezil, rivastigmine and galantamine in the treatment of behavioral and psychological symptoms of Alzheimer's disease.

Methods: Electronic database searches of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were carried out using multiple search terms. Articles included were original publications of randomized, placebo-controlled trials of monotherapy of donepezil, rivastigmine or galantamine that reported a behavioral outcome measure.

Results: 14 studies were identified that matched inclusion criteria. Nine were of donepezil, three of galantamine and two of rivastigmine. Median study treatment length was 24 weeks (range 12–170). Most studies used the Neuropsychiatric Inventory as a behavioral outcome measure although three used specific scales for either agitation or apathy. Four studies were specifically designed to assess behavioral outcomes whilst in the majority of studies behavioral outcomes were only secondary measures. Three studies found statistically significant, albeit modest, differences in the change of NPI total score between drug and placebo. The interpretation of the results of many studies is limited by methodological considerations, including generally low NPI scores at baseline and the investigation of behavioral and psychological symptoms of dementia (BPSD) as secondary outcomes.

Conclusions: The evidence base regarding the efficacy of cholinesterase inhibitors in BPSD is limited, in part due to methodological considerations. In the absence of alternative safe and effective management options, the use of cholinesterase inhibitors is an appropriate pharmacological strategy for the management of BPSD in Alzheimer's disease.

Corresponding author
Correspondence should be addressed to: Dr Joanne Rodda, Department of Mental Health Sciences, University College London, Windeyer Building, 46 Cleveland Street, W1T 4JF, U.K. Phone: +44 (0)1279 827893; Fax: +44 (0)1992 571089 Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

S. E. Black (2007). Donepezil preserves cognition and global function in patients with severe Alzheimer disease. Neurology, 69, 459469.

R. F. Coen , G. R. Swanwick , C. A. O'Boyle and D. Coakley (1997). Behaviour disturbance and other predictors of carer burden in Alzheimer's disease. International Journal of Geriatric Psychiatry, 12, 331336.

J. Cohen-Mansfield (1986). Agitated behaviors in the elderly. II. Preliminary results in the cognitively deteriorated. Journal of the American Geriatrics Society, 34, 722727.

J. Cohen-Mansfield , M. S. Marx and A. S. Rosenthal (1989). A description of agitation in a nursing home. Journal of Gerontology, 44, M77M84.

J. L. Cummings (1997). The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology, 48, S10S16.

J. L. Cummings and C. Back (1998). The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer's disease. American Journal of Geriatric Psychiatry, 6, S64S78.

H. Feldman , S. Gauthier , J. Hecker , B. Vellas , P. Subbiah and E. Whalen (2001). A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease. Neurology, 57, 613620.

S. Gauthier , H. Loft and J. Cummings (2008). Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis. International Journal of Geriatric Psychiatry, 23, 537545.

S. S. Gill (2007). Antipsychotic drug use and mortality in older adults with dementia. Annals of Internal Medicine, 146, 775786.

B. C. Jost and G. T. Grossberg (1996). The evolution of psychiatric symptoms in Alzheimer's disease: a natural history study. Journal of the American Geriatrics Society, 44, 10781081.

H. Kaduszkiewicz , T. Zimmermann , H. P. Beck-Bornholdt and B. H. Van Den (2005). Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. BMJ, 331, 321327.

D. I. Kaufer , J. L. Cummings and D. Christine (1996). Effect of tacrine on behavioral symptoms in Alzheimer's disease: an open-label study. Journal of Geriatric Psychiatry and Neurology, 9, 16.

K. L. Lanctôt , N. Herrmann , R. R. Van , G. Eryavec and C. A. Naranjo (2002). Gender, aggression and serotonergic function are associated with response to sertraline for behavioral disturbances in Alzheimer's disease. International Journal of Geriatric Psychiatry, 17, 531541.

G. Livingston , K. Johnston , C. Katona , J. Paton and C. G. Lyketsos (2005). Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia. American Journal of Psychiatry, 162, 19962021.

K. M. Meehan (2002). Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology, 26, 494504.

M. S. Mega , J. L. Cummings , T. Fiorello and J. Gornbein (1996). The spectrum of behavioral changes in Alzheimer's disease. Neurology, 46, 130135.

A. L. Nyth and C. G. Gottfries (1990). The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders: a Nordic multicentre study. British Journal of Psychiatry, 157, 894901.

J. T. Olin , L. S. Fox , S. Pawluczyk , N. A. Taggart and L. S. Schneider (2001). A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. American Journal of Geriatric Psychiatry, 9, 400405.

B. G. Pollock (2002). Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. American Journal of Psychiatry, 159, 460465.

K. Rockwood , J. Mintzer , L. Truyen , T. Wessel and D. Wilkinson (2001). Effects of a flexible galantamine dose in Alzheimer's disease: a randomised, controlled trial. Journal of Neurology, Neurosurgery and Psychiatry, 71, 589595.

S. Schneeweiss , S. Setoguchi , A. Brookhart , C. Dormuth and P. S. Wang (2007). Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. Canadian Medical Association Journal, 176, 627632.

L. S. Schneider , K. Dagerman and P. S. Insel (2006). Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. American Journal of Geriatric Psychiatry, 14, 191210.

B. Seltzer (2004). Efficacy of donepezil in early-stage Alzheimer disease: a randomized placebo-controlled trial. Archives of Neurolology, 61, 18521856.

S. E. Starkstein , G. Petracca , E. Chemerinski and J. Kremer (2001). Syndromic validity of apathy in Alzheimer's disease. American Journal of Psychiatry, 158, 872877.

P. N. Tariot , P. R. Solomon , J. C. Morris , P. Kershaw , S. Lilienfeld and C. Ding (2000). A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology, 54, 22692276.

P. N. Tariot (2001). A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. Journal of the American Geriatrics Society, 49, 15901599.

B. Winblad (2006). Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study. Lancet, 367, 10571065.

B. Winblad (2007). IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. Neurology, 69, S14S22.

S. Wood (2000). The use of the neuropsychiatric inventory in nursing home residents: characterization and measurement. American Journal of Geriatric Psychiatry, 8, 7583.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 17
Total number of PDF views: 121 *
Loading metrics...

Abstract views

Total abstract views: 781 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 25th June 2017. This data will be updated every 24 hours.