A Risk-Benefit Assessment of Dementia Medications: Systematic Review of the Evidence View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2015-05-05

AUTHORS

Jacob S. Buckley, Shelley R. Salpeter

ABSTRACT

BackgroundThere is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes.ObjectiveOur objective was to review the basis of pharmacological treatments for dementia and to summarize the benefits and risks of dementia treatments.MethodsWe performed a systematic literature search of MEDLINE through November 2014, for English-language trials and observational studies on treatment of dementia and mild cognitive impairment. Additional references were identified by searching bibliographies of relevant publications. Whenever possible, pooled data from meta-analyses or systematic reviews were obtained. Studies were included for review if they were randomized trials or observational studies on dementia or mild cognitive impairment that evaluated efficacy outcomes or adverse outcomes associated with treatment. Studies were excluded if they evaluated non-FDA approved treatments, or if they evaluated treatment in disorders other than dementia and mild cognitive impairment.ResultsThe literature search found 540 potentially relevant studies, of which 257 were included in the systematic review. In pooled trial data, cholinesterase inhibitors (ChEIs) produce small improvements in cognitive, functional, and global benefits in patients with mild to moderate Alzheimer’s and Lewy body dementia, but the clinical significance of these effects are unclear. There is no significant benefit seen for vascular dementia. The efficacy of ChEI treatment appears to wane over time, with minimal benefit seen after 1 year. There is no evidence for benefit for those with advanced disease or those aged over 85 years. Adverse effects are significantly increased with ChEIs, in a dose-dependent manner. A two- to fivefold increased risk for gastrointestinal, neurological, and cardiovascular side effects is related to cholinergic stimulation, the most serious being weight loss, debility, and syncope. Those aged over 85 years have double the risk of adverse events compared with younger patients. Memantine monotherapy may provide some cognitive benefit for patients with moderate to severe Alzheimer’s and vascular dementia, but the benefit is small and may wane over the course of several months. Memantine exhibits no significant benefit in mild dementia or Lewy body dementia or as an add-on treatment with ChEIs. Memantine has a relatively favorable side-effect profile, at least under controlled trial conditions.ConclusionsChEIs produce small, short-lived improvements in cognitive function in mild to moderate dementia, which may not translate into clinically meaningful effects. Marginal benefits are seen with severe disease, long-term treatment, and advanced age. Cholinergic side effects, including weight loss, debility, and syncope, are clinically significant and could be especially detrimental in the frail elderly population, in which the risks of treatment outweigh the benefits. Memantine monotherapy may have minimal benefits in moderate to severe dementia, balanced by minimal adverse effects. More... »

PAGES

453-467

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s40266-015-0266-9

    DOI

    http://dx.doi.org/10.1007/s40266-015-0266-9

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25941104


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    34 schema:description BackgroundThere is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes.ObjectiveOur objective was to review the basis of pharmacological treatments for dementia and to summarize the benefits and risks of dementia treatments.MethodsWe performed a systematic literature search of MEDLINE through November 2014, for English-language trials and observational studies on treatment of dementia and mild cognitive impairment. Additional references were identified by searching bibliographies of relevant publications. Whenever possible, pooled data from meta-analyses or systematic reviews were obtained. Studies were included for review if they were randomized trials or observational studies on dementia or mild cognitive impairment that evaluated efficacy outcomes or adverse outcomes associated with treatment. Studies were excluded if they evaluated non-FDA approved treatments, or if they evaluated treatment in disorders other than dementia and mild cognitive impairment.ResultsThe literature search found 540 potentially relevant studies, of which 257 were included in the systematic review. In pooled trial data, cholinesterase inhibitors (ChEIs) produce small improvements in cognitive, functional, and global benefits in patients with mild to moderate Alzheimer’s and Lewy body dementia, but the clinical significance of these effects are unclear. There is no significant benefit seen for vascular dementia. The efficacy of ChEI treatment appears to wane over time, with minimal benefit seen after 1 year. There is no evidence for benefit for those with advanced disease or those aged over 85 years. Adverse effects are significantly increased with ChEIs, in a dose-dependent manner. A two- to fivefold increased risk for gastrointestinal, neurological, and cardiovascular side effects is related to cholinergic stimulation, the most serious being weight loss, debility, and syncope. Those aged over 85 years have double the risk of adverse events compared with younger patients. Memantine monotherapy may provide some cognitive benefit for patients with moderate to severe Alzheimer’s and vascular dementia, but the benefit is small and may wane over the course of several months. Memantine exhibits no significant benefit in mild dementia or Lewy body dementia or as an add-on treatment with ChEIs. Memantine has a relatively favorable side-effect profile, at least under controlled trial conditions.ConclusionsChEIs produce small, short-lived improvements in cognitive function in mild to moderate dementia, which may not translate into clinically meaningful effects. Marginal benefits are seen with severe disease, long-term treatment, and advanced age. Cholinergic side effects, including weight loss, debility, and syncope, are clinically significant and could be especially detrimental in the frail elderly population, in which the risks of treatment outweigh the benefits. Memantine monotherapy may have minimal benefits in moderate to severe dementia, balanced by minimal adverse effects.
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    41 BackgroundThere
    42 ChEI treatment
    43 ChEIs
    44 English-language trials
    45 Lewy body dementia
    46 MEDLINE
    47 MethodsWe
    48 ObjectiveOur objective
    49 additional references
    50 advanced age
    51 advanced disease
    52 adverse effects
    53 adverse events
    54 adverse outcomes
    55 age
    56 assessment
    57 basis
    58 benefits
    59 bibliography
    60 cardiovascular side effects
    61 cholinergic side effects
    62 cholinergic stimulation
    63 cholinesterase inhibitors
    64 clinical significance
    65 cognitive benefits
    66 cognitive function
    67 cognitive impairment
    68 conditions
    69 course
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    71 data
    72 debility
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    75 dementia treatment
    76 disease
    77 disorders
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    82 elderly population
    83 events
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    86 frail elderly population
    87 function
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    89 global benefits
    90 impairment
    91 improvement
    92 inhibitors
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    94 long-term treatment
    95 loss
    96 manner
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    98 meaningful effect
    99 medications
    100 memantine
    101 memantine monotherapy
    102 mild cognitive impairment
    103 mild dementia
    104 minimal adverse effects
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    106 moderate dementia
    107 monotherapy
    108 months
    109 objective
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