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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... 2003Abnormal involuntary movements known as dyskinesias are amongst the most disabling side-effects of levodopa therapy. It is thought that amantadine, an NMDA-receptor... (Review)
Review
BACKGROUND
Abnormal involuntary movements known as dyskinesias are amongst the most disabling side-effects of levodopa therapy. It is thought that amantadine, an NMDA-receptor antagonist, may reduce dyskinesias in patients with Parkinson's disease without worsening Parkinsonian symptoms.
OBJECTIVES
To compare the efficacy and safety of adjuvant amantadine therapy versus placebo in treating dyskinesia in patients with Parkinson's disease, already established on levodopa, and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted.
SELECTION CRITERIA
Randomised controlled trials comparing amantadine with placebo in the treatment of dyskinesia in patients with a clinical diagnosis of idiopathic Parkinson's disease.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion.
MAIN RESULTS
Three randomised controlled trials were found comparing amantadine with placebo in the treatment of dyskinesia in patients with idiopathic Parkinson's disease. Three trials were excluded on the basis that they had no control group and a further three did not state whether they randomised the treatment that participants received. The included trials were double-blind cross-over studies involving a total of 53 patients. All three studies failed to present data from the first arm, instead presenting results as combined data from both treatment arms and both placebo arms. Two trials had no wash-out interval between the treatment periods. In view of the risk of a carry-over effect into the second arm, the results of these trials were not analysed. The final trial had a one week wash-out interval but only examined 11 participants. One study reported side-effects of amantadine in 8 of the 18 participants, including confusion and worsening of hallucinations. Another reported reversible edema of both feet in one of eleven participants.
REVIEWER'S CONCLUSIONS
Due to lack of evidence it is impossible to determine whether amantadine is a safe and effective form of treatment for levodopa-induced dyskinesias in patients with Parkinson's disease.
Topics: Amantadine; Antiparkinson Agents; Dyskinesias; Humans; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 12804468
DOI: 10.1002/14651858.CD003467 -
The Cochrane Database of Systematic... 2003Although levodopa is the most common drug prescribed to relieve the symptoms of Parkinson's disease it is associated with motor and psychiatric side-effects.... (Review)
Review
BACKGROUND
Although levodopa is the most common drug prescribed to relieve the symptoms of Parkinson's disease it is associated with motor and psychiatric side-effects. Consequently, interest has turned to alternative drugs with improved side-effect profiles to replace or augment levodopa. Amantadine, originally used as an antiviral drug, has been shown to improve the symptoms of Parkinson's disease.
OBJECTIVES
To compare the efficacy and safety of amantadine therapy (monotherapy or adjuvant therapy) versus placebo in treating people with Parkinson's disease.
SEARCH STRATEGY
Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted.
SELECTION CRITERIA
Randomised controlled trials comparing amantadine with placebo in the treatment of patients with a clinical diagnosis of idiopathic Parkinson's disease.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion.
MAIN RESULTS
Six randomised controlled trials were found comparing amantadine monotherapy or adjuvant therapy with placebo in the treatment of idiopathic Parkinson's disease. Five examined amantadine as adjuvant therapy with optimal levels of levodopa or anticholinergics and one examined amantadine as an adjuvant therapy with minimum tolerated levels of anticholinergics or as a monotherapy. Five were double-blind cross-over studies and one was a double-blind parallel group study. In total they examined 215 patients. The parallel group study allowed the randomisation codes to be broken and allowed patients in the placebo group to then receive amantadine. This could have led to bias. One study did not present the results of the placebo arm of the trial, hence we could not determine the difference between the two treatment groups. Two cross-over studies presented the results of the combined data from both treatment and placebo arms. The risk of carry-over effect into the second arm meant that these results could not be analysed. The final two studies presented at least some of their data from the end of the first arm of the trials. However only means were given, without standard deviations, so we could not determine the statistical significance of any difference between the amantadine and placebo groups. Although the authors did report on the side-effects from amantadine (such as livido recticularis, dry mouth and blurred vision), they state that none of them were severe.
REVIEWER'S CONCLUSIONS
A considerable amount of evidence on the effectiveness of amantadine has accrued from non-controlled trials, often in patients with Parkinsonian conditions other than idiopathic Parkinson's disease. However, rigorous analysis of the six randomised controlled trials of amantadine reveals insufficient evidence of its efficacy and safety in the treatment of idiopathic Parkinson's disease.
Topics: Amantadine; Antiparkinson Agents; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 12535476
DOI: 10.1002/14651858.CD003468 -
Health Technology Assessment... 2000Multiple sclerosis (MS) is an important problem both for people with the disease and for society. There is no cure, and alleviation of symptoms forms the cornerstone of... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is an important problem both for people with the disease and for society. There is no cure, and alleviation of symptoms forms the cornerstone of care. Excessive fatigue that severely limits activity is experienced by at least two-thirds of the estimated 60,000 people with MS in the UK.
OBJECTIVES
(1) To identify current treatments for fatigue in MS and their evidence-base. (2) To systematically review the evidence for those treatments that have been investigated in more than one rigorous study, in order to determine their effectiveness and cost-effectiveness.
METHODS
The review was carried out in two stages: a formal scoping review (to assess the range of interventions used by people with MS), and a systematic review for treatments that had been identified as promising and that had been investigated in clinical trials (as identified in the scoping review). A systematic review of research on costs and cost-effectiveness of those interventions identified as promising was also performed. Electronic databases, including MEDLINE and EMBASE, were searched for the period 1991-June 1999 (scoping review) and 1966-December 1999 (systematic review). Reference lists from publications were also searched, and experts were contacted for any additional information not already identified.
RESULTS
Interventions identified for the treatment of fatigue in MS (1) Behavioural advice. This is the main element of initial clinical management and no rigorous research of its effectiveness was identified. (2) Drugs (amantadine, pemoline, potassium-channel blockers and antidepressants). (3) Training, rehabilitation and devices (cooling vests and electromagnetic fields). (4) Alternative therapies (bee venom, cannabis, acupuncture/acupressure and yoga). Only two drugs, amantadine and pemoline, met the criteria for full systematic review. RESULTS - EFFECTIVENESS OF AMANTADINE: One parallel and three crossover trials were found, involving a total of 236 people with MS. All studies were open to bias. All studies showed a pattern in favour of amantadine compared with placebo, but there is considerable uncertainty about the validity and clinical significance of this finding. This pattern of benefit was considerably undermined when different assumptions were used in the sensitivity analysis. RESULTS - EFFECTIVENESS OF PEMOLINE: One parallel and one crossover trial were found involving a total of 126 people with MS. Both studies were open to bias. There was no overall tendency in favour of pemoline over placebo and an excess of reports of adverse effects with pemoline. RESULTS - HEALTH ECONOMIC ANALYSIS: The drug costs of amantadine and pemoline are modest (pound 200 and pound 80 per annum, respectively). No economic evaluations were identified in the systematic review, and available data were insufficient to allow modelling of cost-effectiveness in this rapid review.
CONCLUSIONS
There is insufficient evidence to allow people with MS, clinicians or policy makers to make informed decisions on the appropriate use of the many treatments on offer. Only amantadine appears to have some proven ability to alleviate the fatigue in MS, though only a proportion of users will obtain benefit and then only some of these patients will benefit sufficiently to take the drug in the long term. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: The frequency, severity and impact of fatigue, the poverty of available research, and the absence of any ongoing research, suggest that new research is an urgent priority. People with MS, clinicians and policy makers should work together to ensure that the evidence required is collected as quickly as possible by encouraging involvement in rigorous research. Research should not be restricted to the two drugs reviewed in depth in this report. All interventions identified in the scoping review (see above) should be considered, as should basic scientific research into the underlying mechanism of fatigue in MS.
Topics: Amantadine; Central Nervous System Stimulants; Cost-Benefit Analysis; Dopamine Agents; Evidence-Based Medicine; Fatigue; Humans; Multiple Sclerosis; Pemoline
PubMed: 11074395
DOI: No ID Found