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44 Interventions in Alzheimer’s Disease KCE Reports 111 Key Points Ginkgo biloba • Recent systematic reviews conclude the evidence that Ginkgo biloba has predictable and clinically significant benefit for people with dementia is inconsistent and unreliable. Also in MCI no indications of efficacy were found. Inhibitors of acetylcholinesterase (ChEIs) • ChEIs significantly improve cognitive function from a statistical point of view. Around 10 patients need to be treated for each clinically detectable improvement. The CIBIC+ is improved or maintained in 57-75% of patients versus 42-56% of placebo patients. • For all 3 ChEIs, there are indications of a minor benefit in activities of daily living. No interpretable data were available (or no indication of benefit for donepezil) for prevention of placement in a nursing home (institutionalisation). • Both effects and adverse event rates (mainly anorexia, nausea, vomiting and diarrhoea) are dose-dependent. After drug discontinuation both effects and side-effects disappear. Memantine • The effect of memantine monotherapy on cognitive function is small, or even not statistically significant. • The improvements in clinician’s global impression, ADL and for psychopathology are minor. The clinical relevance of these findings is questionable. The data collected for memantine on reduction in degree of care by caregivers or institutions were not made public, nor were data made public for the endpoint prevention of institutionalisation. • Two RCTs in which memantine was combined for 6 months with ChEIs in AD patients with a MMSE 3-14 reported positive results for cognitive function and CIBIC+ versus ChEI monotherapy, but this was not confirmed in a similar trial in AD patients with a MMSE 10-22. Antipsychotics and antidepressants • It is now well established that the use of both typical and atypical antipsychotics in patients with dementia is associated with an increased mortality rate and that their use should be restricted, eg to hostile, aggressive patients. • The optimal diagnosis and management of depression in AD patients is not well-defined.
KCE Reports 111 Interventions in Alzheimer’s Disease 45 5 COST-EFFECTIVENESS OF ALZHEIMER’S DISEASE INTERVENTIONS: REVIEW OF THE LITERATURE. 5.1 REVIEW METHODS 5.1.1 Literature search strategies The strategies for searching the literature were aimed at providing an answer to the following questions of interest: • Is there scientific evidence to support the cost-effectiveness of pharmacologic treatments in Alzheimer’s patients? • Is there scientific evidence to support the cost-effectiveness of nonpharmacological treatments in Alzheimer or dementia’s patients? The searches for the published economic literature were performed by consulting various databases up to the end of August 2008. 5.1.1.1 Health technology assessment (HTA) reports The CRD HTA database was consulted to retrieve HTA reports using the search terms “MeSH Alzheimer Disease EXPLODE 1 2 3” or “MeSH Dementia EXPLODE 1 2”. The websites of the HTA institutes listed in the International Network of Agencies for Health Technology Assessment (INAHTA) website were also consulted to retrieve additional references. Seventy-nine (79) citations were returned from the CRD HTA database for both Alzheimer disease and Dementia. The search on the HTA websites allowed the identification of one additional citation. 21 5.1.1.2 Economic evaluations and reviews of economic evaluations The NHS EED(CRD), Medline(OVID), EMBASE and Econlit(OVID) databases were searched to identify full economic evaluations and reviews of full economic evaluations of non-pharmacologic and pharmacologic treatments for Alzheimer’s disease patients, and of non-pharmacologic treatments for Dementia patients. The search was restricted to articles published after 2004, which corresponds to the time limit of the literature review performed by Loveman et al., 72 an HTA report identified in the pre-assessment phase of this project. No restrictions on language were imposed. The details of the search strategies used in each database for each research question are provided in appendix. A brief description of the search results is provided here (Table 7): Table 7: Summary of the results of the cost-effectiveness literature searches Database Date of database search Number of citations identified Pharmacologic and non-pharmacologic treatment in AD patients CRD EED January 2004 – August 2008 50 OVID MEDLINE January 2004 – August 2008 235 EMBASE January 2004 – August 2008 333 OVID ECONLIT January 2004 – August 2008 1 Total 619 Non-pharmacologic treatment in dementia patients CRD EED January 2004 – September 2008 36 OVID MEDLINE January 2004 – September 2008 41
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