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The Cochrane Database of Systematic... 2002Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their potential value and... (Review)
Review
BACKGROUND
Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects.
OBJECTIVES
The objective of this review was to assess the effects and safety of amantadine and rimantadine in healthy adults.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE and reference lists of articles. We also contacted manufacturers, researchers and authors.
SELECTION CRITERIA
Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults.
DATA COLLECTION AND ANALYSIS
For prevention trials the numbers of participants with clinically defined influenza, with serologically confirmed clinical influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever and adverse effects.
MAIN RESULTS
Amantadine prevented 23% of clinical influenza cases (95% confidence interval 11% to 34%), and 63% of serologically confirmed clinical influenza A cases (95% confidence interval 42% to 76%). Amantadine reduced duration of fever by one day (95% confidence interval 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine.
REVIEWER'S CONCLUSIONS
Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine. [This abstract has been prepared centrally.]
Topics: Adult; Aged; Amantadine; Antiviral Agents; Drug Administration Schedule; Humans; Influenza A virus; Influenza, Human; Middle Aged; Randomized Controlled Trials as Topic; Rimantadine
PubMed: 12137620
DOI: 10.1002/14651858.CD001169 -
The Cochrane Database of Systematic... 2001Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their properties and... (Review)
Review
BACKGROUND
Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their properties and concerns about possible adverse effects.
OBJECTIVES
The objective of this review was to assess the effects and safety of amantadine and rimantadine in healthy adults.
SEARCH STRATEGY
We searched the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We also contacted manufacturers, researchers and authors.
SELECTION CRITERIA
Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults.
DATA COLLECTION AND ANALYSIS
For prevention trials the numbers of participants with clinically defined influenza, with serologically confirmed clinical influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever and adverse effects.
MAIN RESULTS
Amantadine prevented 23% of clinical influenza cases (95% confidence interval 11% to 34%), and 63% of serologically confirmed clinical influenza A cases (95% confidence interval 42% to 76%). Amantadine reduced duration of fever by one day (95% confidence interval 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system adverse and study withdrawals were significantly more common with amantadine than rimantadine.
REVIEWER'S CONCLUSIONS
Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine.
Topics: Adult; Aged; Amantadine; Antiviral Agents; Drug Administration Schedule; Humans; Influenza A virus; Influenza, Human; Middle Aged; Randomized Controlled Trials as Topic; Rimantadine
PubMed: 11405978
DOI: 10.1002/14651858.CD001169 -
The Cochrane Database of Systematic... May 2012Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS... (Review)
Review
BACKGROUND
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients.
OBJECTIVES
To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose.
SEARCH METHODS
A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied.
SELECTION CRITERIA
Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included.
DATA COLLECTION AND ANALYSIS
Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up.
MAIN RESULTS
The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported.
AUTHORS' CONCLUSIONS
There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.
Topics: Acetylcarnitine; Adult; Amantadine; Fatigue; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 22592719
DOI: 10.1002/14651858.CD007280.pub3 -
Annals of Internal Medicine Apr 2012Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza.
PURPOSE
To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza.
DATA SOURCES
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists.
STUDY SELECTION
Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness.
DATA EXTRACTION
Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.
DATA SYNTHESIS
74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine.
LIMITATIONS
Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias.
CONCLUSION
Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.
Topics: Administration, Inhalation; Administration, Oral; Amantadine; Antiviral Agents; Confounding Factors, Epidemiologic; Hospitalization; Humans; Influenza, Human; Oseltamivir; Rimantadine; Treatment Outcome; Zanamivir
PubMed: 22371849
DOI: 10.7326/0003-4819-156-7-201204030-00411 -
The Cochrane Database of Systematic... Feb 2010Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS... (Review)
Review
BACKGROUND
Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients.
OBJECTIVES
To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose.
SEARCH STRATEGY
A literature search was performed using Cochrane MS Group Trials Register (21 May 2009), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2009, issue 2, MEDLINE (PubMed) (1966-21 May 2009), EMBASE (1974-21 May 2009). Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied.
SELECTION CRITERIA
Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults with a clinical diagnosis of fatigue associated with multiple sclerosis were included.
DATA COLLECTION AND ANALYSIS
Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer however this was not necessary. The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up.
MAIN RESULTS
The search identified one randomized cross-over trial. In this study patients were exposed to both acetyl L-carnitine (ALCAR(tm)) 2 grams daily and amantadine 200 mg daily in adult patients with relapsing-remitting and secondary progressive MS. The effects of carnitine on fatigue are not clear based on the one included crossover RCT. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55. Mortality, serious adverse events, total adverse events, and quality of life were not reported.
AUTHORS' CONCLUSIONS
There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators.
Topics: Acetylcarnitine; Adult; Fatigue; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 20166093
DOI: 10.1002/14651858.CD007280.pub2 -
The Cochrane Database of Systematic... Oct 2004Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of L-glutamate plays a role in the pathogenesis of Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may prevent excitatory amino acid neurotoxicity without interfering with the physiological actions of glutamate required for memory and learning.
OBJECTIVES
To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, or vascular or mixed dementia.
SEARCH STRATEGY
Trials were identified from a search of the Trial-based Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 April 2004 using the terms: memantin*, namenda*, ebixa*, axura*, D-145, DMAA, DRG-0267. All major health care databases and many ongoing trial databases are searched regularly to keep this Register up to date.
SELECTION CRITERIA
Double-blind, parallel group, placebo-controlled, randomised and unconfounded trials in which memantine was administered to people with dementia.
DATA COLLECTION AND ANALYSIS
Data were extracted, pooled where possible, and weighted mean differences, standardized mean differences or odds ratios were estimated. Intention-to-treat (ITT) and observed cases (OC) analyses are reported, where data were available.
MAIN RESULTS
The evidence suggests that memantine has a positive effect on cognition, mood and behaviour and the ability to perform activities of daily living in patients with moderate to severe Alzheimer's disease. The results in patients with mild to moderate vascular dementia, suggest a beneficial effect of 20mg/day of memantine on cognitive function measured at 28 weeks. However, these results are neither supported by an effect on ability to perform activities of daily living nor by an effect on the clinical impression of change. This suggests that, in patients with mild to moderate vascular dementia, the effect on cognitive function is not translated into clinically detectable changes.
REVIEWERS' CONCLUSIONS
:Memantine 20 mg/day caused a clinically noticeable reduction in deterioration over 28 weeks in patients with moderate to severe Alzheimer disease. This was supported by less functional and cognitive deterioration. Patients taking memantine were less likely to become agitated. The effect in mild to moderate AD is unknown. Patients with mild to moderate vascular dementia receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but the effects were not clinically discernible. There is an early beneficial effect on cognition, mood, behaviour and clinical impression for memantine at 6 weeks. The drug is well tolerated in general and the incidence of adverse effects is low.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Dementia; Dementia, Vascular; Excitatory Amino Acid Antagonists; Humans; Memantine; Randomized Controlled Trials as Topic
PubMed: 15495043
DOI: 10.1002/14651858.CD003154.pub2 -
Canadian Respiratory Journal Oct 2003To evaluate the efficacy and safety of amantadine and rimantadine, the first generation antivirals, for the prophylaxis of influenza virus. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the efficacy and safety of amantadine and rimantadine, the first generation antivirals, for the prophylaxis of influenza virus.
DATA SOURCES
A systematic search of the English language literature using MEDLINE, EMBASE, Current Contents and the Cochrane database from 1966 to April 2002, as well as a manual search of references from retrieved articles, were performed.
STUDY SELECTION
Prospective, randomized, controlled clinical trials evaluating amantadine and rimantadine for prophylaxis of naturally occurring influenza A illness were considered. The control arm used either a placebo or an antiviral agent.
DATA EXTRACTION
Each trial was assessed by two authors to determine the adequacy of randomization and description of withdrawals. Efficacy data were extracted according to a predefined protocol. Discrepancies in data extraction among the investigators were solved by consensus. Nine prophylaxis studies of amantadine and rimantadine met the criteria for this systematic review.
DATA SYNTHESIS
Seven amantadine versus placebo trials (n=1797), three rimantadine versus placebo trials (n=688) and two amantadine versus rimantadine studies (n=455) were included for the meta-analysis on the prevention of influenza A illness. The summary of results for the relative odds of illness indicated a 64% reduction in the amantadine group compared with placebo (OR 0.36, 95% CI 0.23 to 0.55, P< or =0.001), a 75% reduction in illness for the rimantadine group compared with placebo (OR 0.25, 95% CI 0.07 to 0.97, P=0.05) and no significant differences in the odds of illness for the amantadine versus rimantadine groups (OR 1.15, 95% CI 0.57 to 2.32, P=0.32). The summary of results examining adverse events showed significantly higher odds of central nervous system adverse reactions and premature withdrawal from the clinical trials in the amantadine-treated group than in the placebo-treated group. Compared with the placebo-treated group, the rimantadine-treated group did not have a significantly higher rate of withdrawal or central nervous system events. However, there was a significant increase in the odds of gastrointestinal adverse events for those treated with rimantadine compared with those treated with placebo (OR 3.34, 95% CI 1.17 to 9.55, P=0.03). In the comparative trials of amantadine to rimantadine, rimantadine was associated with an 82% reduction in the odds of central nervous system events (OR 0.18, 95% CI 0.03 to 1.00, P=0.05) and a 60% reduction in the odds of discontinuing treatment (OR 0.40, 95% CI 0.20 to 0.79, P=0.009).
CONCLUSION
This meta-analysis demonstrates that amantadine and rimantadine are superior to placebo in the prevention of influenza A illness. Both antiviral agents have an increased number of adverse events compared with placebo; however, the use of amantadine is associated with significantly higher numbers of central nervous system events and treatment withdrawals compared with rimantadine. Thus, rimantadine should be the preferred agent in this class for the prevention of influenza A virus infection and should be made available in Canada.
Topics: Amantadine; Antiviral Agents; Canada; Data Interpretation, Statistical; Drug Administration Schedule; Humans; Influenza A virus; Influenza, Human; Randomized Controlled Trials as Topic; Rimantadine
PubMed: 14571290
DOI: 10.1155/2003/453183 -
The Cochrane Database of Systematic... Nov 2010In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients fatigue can be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients fatigue can be severely debilitating, thereby impacting daily activity and quality of life, often with rest not counteracting fatigue. Fatigue frequently occurs in patients with advanced disease and modalities treating cancer often contribute or cause fatigue. Further complicating issues are its multidimensionality, subjective nature, and lack of a consensus definition of fatigue. Pathophysiology is not fully understood and evidence-based treatment approaches are needed.
OBJECTIVES
The objective was to determine efficacy of pharmacological treatments on non-specific fatigue in palliative care. The focus was on patients at an advanced stage of disease, including cancer and other chronic diseases associated with fatigue, aiming to relieve fatigue. Studies aiming at curative treatment (e.g. surgical intervention for early breast cancer) were not included.
SEARCH STRATEGY
We searched EMBASE; Psych Lit, CENTRAL and MEDLINE to June 2009.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) concerning adult palliative care with focus on pharmacological treatment of fatigue. The primary outcome had to be non-specific fatigue (or related terms such as asthenia).
DATA COLLECTION AND ANALYSIS
Results were screened and included if they met the selection criteria. If two or more studies were identified that investigated a specific drug in a population with the same disease, meta-analysis was conducted. In addition, comparison of type of drug investigated in a specific population as well as comparison of frequent adverse effects of fatigue treatment was done by creating overview tables.
MAIN RESULTS
More than 2000 publications were screened, and 22 met inclusion criteria. In total, data from 11 drugs and 1632 participants were analysed. Studies investigating amantadine, pemoline, and modafinil in participants with Multiple Sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue could be used for meta-analysis. Amantadine in MS and methylphenidate in cancer patients showed a superior effect. Most studies had low participant numbers and were heterogenous.
AUTHORS' CONCLUSIONS
Based on limited evidence, we cannot recommend a specific drug for treatment of fatigue in palliative care patients. Surprisingly, corticosteroids have not been a research focus for fatigue treatment, although these drugs are frequently used. Recent fatigue research seems to focus on modafinil, which may be beneficial although there is no evidence currently. Amantadine and methylphenidate should be further examined. Consensus regarding fatigue assessment in advanced disease is needed.
Topics: Adult; Amantadine; Benzhydryl Compounds; Central Nervous System Stimulants; Fatigue; Humans; Kidney Failure, Chronic; Methylphenidate; Modafinil; Multiple Sclerosis; Neoplasms; Palliative Care; Pemoline; Randomized Controlled Trials as Topic
PubMed: 21069692
DOI: 10.1002/14651858.CD006788.pub2 -
Therapeutic Advances in... Aug 2012The objective of this study was to conduct a systematic review and meta-analysis of randomized placebo-controlled trials of amantadine for the treatment of...
OBJECTIVE
The objective of this study was to conduct a systematic review and meta-analysis of randomized placebo-controlled trials of amantadine for the treatment of olanzapine-induced weight gain.
METHODS
Studies were identified using online searches of PUBMED/MEDLINE and Cochrane database (CENTRAL), along with websites recording trial information such as ClinicalTrials.gov, Controlled-trials.com, and Clinicalstudyresults.org. Study eligibility criteria included randomized, double-blind clinical trials comparing amantadine with placebo for olanzapine-induced weight gain with body weight as an outcome measure and study duration of at least 12 weeks. The methodological quality of included trials was assessed using the Jadad Scale. Separate meta-analyses were undertaken for each outcome (body weight and frequency of weight loss >7%) and treatment effects were expressed as weighted mean differences (WMD) and Mantel-Haenszel odds ratio for continuous and categorical outcomes, respectively.
RESULTS
A systematic review of literature revealed six studies that had assessed amantadine for olanzapine-induced weight gain. Of these, two studies (n = 144) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight and frequency of body weight loss >7%. For body weight change, WMD was -1.85 (95% confidence interval [CI] -3.31 to -0.39) kg with amantadine as compared with placebo; the overall effect was statistically significant (p = 0.01). For frequency of body weight loss >7%, Mantel-Haenszel odds ratio for weight loss was 3.72 (95% CI 1.19-11.62), favoring amantadine as compared with placebo, and the overall effect was significant (p = 0.02).
CONCLUSIONS
Existing data is limited to two studies, which support the efficacy of amantadine for olanzapine-induced weight gain and a significant proportion of patients might lose weight with amantadine compared with placebo.
PubMed: 23983968
DOI: 10.1177/2045125312440441 -
The Cochrane Database of Systematic... Apr 2006Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia.
OBJECTIVES
To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia.
SEARCH STRATEGY
The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 8th February 2006. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition, the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries.
SELECTION CRITERIA
Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia.
DATA COLLECTION AND ANALYSIS
Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported.
MAIN RESULTS
1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (2.97 points on the 100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. Pooled data from three unpublished studies indicate a marginal beneficial effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25, P = 0.03) but no effect on behaviour, activities of daily living or OC analysis of cognition.3. Mild to moderate vascular dementia. Pooled data from two six month studies indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There is no evidence either way about whether it has an effect on agitation which is already present.5. Memantine is well tolerated.
AUTHORS' CONCLUSIONS
Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Cognition Disorders; Dementia; Dementia, Vascular; Excitatory Amino Acid Antagonists; Humans; Memantine; Randomized Controlled Trials as Topic
PubMed: 16625572
DOI: 10.1002/14651858.CD003154.pub5