The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease

Holmes, Clive; Wilkinson, David; Dean, Christine; Vethanayagam, S.; Olivieri, Stefano; Langley, Alison; Pandita-Gunawardena, N. D.; Hogg, Florence; Clare, Corinne; Damms, J.

doi:10.1212/01.wnl.0000129990.32253.7b

Cited by 309 publications

(183 citation statements)

References 20 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…Cholinesterase inhibitors and memantine have been reported to have small-to-medium effect size effects on neuropsychiatric symptoms, including psychosis and agitation; however, these data were obtained from secondary outcome measures and post hoc analyses of patients who often did not have clinically significant behavioral symptoms at baseline, and yet other trials have shown no effect of cognitive enhancers on behavior (Cummings et al, 2006a, b;Sink et al, 2005;McKeith et al, 2000;Trinh et al, 2003;Hermann et al, 2005). A prospective trial of donepezil for neuropsychiatric symptoms in outpatients with mildmoderate AD showed improvement in global neuropsychiatric symptoms during open-label treatment for 3 months, followed by symptomatic worsening only in placebo-treated patients during the subsequent randomized discontinuation phase of the trial (Holmes et al, 2004). Yet, these patients had relatively modest levels of behavioral symptoms.…”

Section: Other Psychotropicsmentioning

confidence: 99%

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Jeste

Blazer

Casey

et al. 2007

Neuropsychopharmacol

329

273

View full text Add to dashboard Cite

In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6-1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a 'black box' warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/ or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.

show abstract

Section: Other Psychotropicsmentioning

confidence: 99%

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

Jeste

Blazer

Casey

et al. 2007

Neuropsychopharmacol

329

273

View full text Add to dashboard Cite

show abstract

“…In spite of this, the AChEIs may differ in their individual profiles, as the SPCs report agitation as a common AE (1-10%) with donepezil and rivastigmine treatment but rare with galantamine (0.01-0.1%) (Aricept SPC, 2007;Reminyl Tablets SPC, 2007;Exelon Capsules SPC, 2008). Furthermore, AChEIs have not consistently demonstrated a specific benefit on agitation in dementia (Gauthier et al, 2002;Holmes et al, 2004;Sink et al, 2005;Black et al, 2007;Howard et al, 2007).…”

Section: Agitationmentioning

confidence: 99%

A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors

Jones¹

2010

Int J Geriat Psychiatry

View full text Add to dashboard Cite

Objective: Alzheimer's disease (AD) is prevalent among elderly people, who often have comorbid conditions, and may be prescribed multiple medications. Drug safety and tolerability is paramount in maximising efficacy and optimising patient and carer quality of life, as patients are vulnerable to adverse events (AEs) and/or compliance difficulties. The two principal categories of drug used in the treatment of AD are the acetylcholinesterase inhibitors (AChEIs) and the NMDA-receptor antagonist, memantine. This paper reviews the most recent safety data for memantine in comparison with the AChEIs. Design: Review of most recent safety/tolerability data for memantine and AChEIs, derived from metaanalyses, pooled analyses, European SPCs and EMEA publications. Results: Memantine was found to have a favourable tolerability profile when used as monotherapy or in combination with other agents. AChEIs were found to be fairly well tolerated. All treatments commonly or very commonly produce dizziness and/or headache. AChEIs are associated with many more types of AEs than memantine, particularly in the gastrointestinal category. Agitation is a less common AE when comparing memantine treatment to placebo, but just as common when comparing AChEI treatment to placebo. Withdrawals in memantine-treated groups are comparable to placebo, and more common in AChEI-treated groups compared to placebo. Overall, drug-drug interactions, contraindications and warnings were fewer for memantine than AChEIs. Conclusions: In both the clinical and naturalistic setting, memantine displays a safety and tolerability profile that is favourable and distinct from that of AChEIs. Safety and tolerability profiles should be given careful consideration when selecting treatment for AD patients.

show abstract

“…One included trial 43 allowed the inclusion of patients with vascular dementia; however, the predominant disorder was AD and therefore the trial met the present review inclusion criteria (see Appendix 2). Eight published RCTs were parallel comparisons of donepezil with placebo, 41,[43][44][45][46][47][48][49] three RCTs compared two doses of donepezil with placebo, [50][51][52] one compared three doses of donepezil with placebo 53 and one was a crossover comparison of donepezil with placebo. 54 One unpublished RCT reports data on participants with mild AD.…”

Section: Donepezil Quantity and Quality Of Researchmentioning

confidence: 99%

The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's disease

Loveman

Green²,

Kirby³

et al. 2006

Health Technol Assess

164

114

View full text Add to dashboard Cite

Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per monograph and for the rest of the world £3 per monograph.You can order HTA monographs from our Despatch Agents:-fax (with credit card or official purchase order) -post (with credit card or official purchase order or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you either to pay securely by credit card or to print out your order and then post or fax it. NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of £100 for each volume (normally comprising 30-40 titles). The commercial subscription rate is £300 per volume. Please see our website for details. Subscriptions can only be purchased for the current or forthcoming volume. Contact details are as follows: Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd and drawn on a bank with a UK address. Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard, Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email. Paying by official purchase orderYou can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK. We cannot at present accept purchase orders from commercial companies or from outside the UK. How do I get a copy of HTA on CD?Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (see contact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.The website also provides information about the HTA Programme and lists the membership of the various committees. HTAThe clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's disease NHS R&D HTA ProgrammeT he research findings from the NHS R&D Health Technology Assessment (HTA) Programme directly influence key decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC) who rely on HTA outputs to help raise standards of care. HTA findings also help to improve the quality of the service in the NHS indirectly in that they form a key component of the 'National Knowledge Service' that is being developed to improve the evidence of clinical practice throughout the NHS.The HTA Programme was set up in 1993. Its role is to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined to include all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care, rather than settings of care.The HTA Programme commissions research only on topics where it has identified key ...

show abstract

The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease

Abstract: Donepezil has significant efficacy in the treatment of neuropsychiatric symptoms in patients with mild to moderate AD.

Cited by 309 publications

References 20 publications

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia

A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors

The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's disease

Contact Info

Product

Resources

About