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The Cochrane Database of Systematic... Aug 2022Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness.
OBJECTIVES
To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence).
AUTHORS' CONCLUSIONS
It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Female; Humans; Male; Memantine; Odds Ratio; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36006807
DOI: 10.1002/14651858.CD013845.pub2 -
The Cochrane Database of Systematic... Jan 2012The effectiveness and safety of amantadine (AMT) and rimantadine (RMT) for preventing and treating influenza A in adults has been systematically reviewed. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The effectiveness and safety of amantadine (AMT) and rimantadine (RMT) for preventing and treating influenza A in adults has been systematically reviewed. However, little is known about these treatments in children and the elderly.
OBJECTIVES
To systematically review the effectiveness and safety of AMT and RMT in preventing and treating influenza A in children and the elderly.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2) which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1966 to June week 3, 2011) and EMBASE (1980 to June 2011).
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing AMT and/or RMT with placebo, control, other antivirals or different doses or schedules of AMT or RMT, or both, or no intervention, in children and the elderly.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and assessed methodological quality. We resolved disagreements by consensus. In all comparisons except for one, we separately analysed the trials in children and the elderly using Review Manager software.
MAIN RESULTS
A total of 12 studies involving 2494 participants (1586 children and adolescents and 908 elderly) compared AMT and RMT with placebo, paracetamol (one trial; 69 children) or zanamivir (two trials; 545 seniors). All studies were RCTs but most were still susceptible to bias. Two trials in the elderly had a high risk of bias because of incomplete outcome data. In one of those trials there was also a lack of outcome assessment blinding. Risk of bias was unclear in 10 studies due to unclear random sequence generation and allocation concealment. Only two trials in children were considered to have a low risk of bias.AMT was effective in preventing influenza A in children. A total of 773 participants were included in this outcome (risk ratio (RR) 0.11; 95% confidence interval (CI) 0.04 to 0.30). The assumed risk of influenza in the control group was 10 per 100 and the corresponding risk in the RMT group was one per 100 (95% CI 0 to 3). The quality of the evidence was considered low. For treatment purposes, RMT was beneficial for abating fever on day three of treatment. For this purpose one study was selected with low risk of bias and included 69 children (RR 0.36; 95% CI 0.14 to 0.91). The assumed risk was 38 per 100 and the corresponding risk in the RMT group was 14 per 100, 95% CI 5 to 34. The quality of the evidence was moderate.RMT did not show a prophylactic effect against influenza in the elderly, but the quality of evidence was considered very low. There were 103 participants (RR 0.45; 95% CI 0.14 to 1.41, for an assumed risk of 17 per 100 and a corresponding risk in the RMT group of 7 per 100, 95% CI 2 to 23). We did not identify any AMT trials in the elderly that met our inclusion criteria.There was no evidence of adverse effects of AMT and RMT in children or an adverse effect of RMT in the elderly. We did not identify any AMT trials in the elderly that met our inclusion criteria.
AUTHORS' CONCLUSIONS
AMT is effective in preventing influenza A in children but the NNTB is high (NNTB: 12 (95% CI 9 to 17). RMT probably helps the abatement of fever on day three of treatment, but the quality of the evidence is poor. Due to the small number of available studies, we could not reach a definitive conclusion on the safety of AMT or the effectiveness of RMT in preventing influenza in children and the elderly.
Topics: Adolescent; Aged; Amantadine; Antiviral Agents; Child; Humans; Influenza A Virus, H1N1 Subtype; Influenza A virus; Influenza, Human; Randomized Controlled Trials as Topic; Rimantadine; Sex Factors; Young Adult
PubMed: 22258950
DOI: 10.1002/14651858.CD002745.pub3 -
The Cochrane Database of Systematic... May 2015Postpolio syndrome (PPS) may affect survivors of paralytic poliomyelitis and is characterised by a complex of neuromuscular symptoms leading to a decline in physical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpolio syndrome (PPS) may affect survivors of paralytic poliomyelitis and is characterised by a complex of neuromuscular symptoms leading to a decline in physical functioning. The effectiveness of pharmacological treatment and rehabilitation management in PPS is not yet established. This is an update of a review first published in 2011.
OBJECTIVES
To systematically review the evidence from randomised and quasi-randomised controlled trials for the effect of any pharmacological or non-pharmacological treatment for PPS compared to placebo, usual care or no treatment.
SEARCH METHODS
We searched the following databases on 21 July 2014: Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL Plus. We also checked reference lists of all relevant articles, searched the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment (HTA) Database and trial registers and contacted investigators known to be involved in research in this area.
SELECTION CRITERIA
Randomised and quasi-randomised trials of any form of pharmacological or non-pharmacological treatment for people with PPS. The primary outcome was self perceived activity limitations and secondary outcomes were muscle strength, muscle endurance, fatigue, pain and adverse events.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included 10 pharmacological (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine, amantadine, prednisone) and three non-pharmacological (muscle strengthening, rehabilitation in a warm climate (that is temperature ± 25°C, dry and sunny) and a cold climate (that is temperature ± 0°C, rainy or snowy), static magnetic fields) studies with a total of 675 participants with PPS in this review. None of the included studies were completely free from any risk of bias, the most prevalent risk of bias being lack of blinding.There was moderate- and low-quality evidence that IVIg has no beneficial effect on activity limitations in the short term and long term, respectively, and inconsistency in the evidence for effectiveness on muscle strength. IVIg caused minor adverse events in a substantial proportion of the participants. Results of one trial provided very low-quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations without generating adverse events. Data from two single trials suggested that muscle strengthening of thumb muscles (very low-quality evidence) and static magnetic fields (moderate-quality evidence) are safe and beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. Finally, there was evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS.
AUTHORS' CONCLUSIONS
Due to insufficient good-quality data and lack of randomised studies, it was impossible to draw definite conclusions about the effectiveness of interventions for PPS. Results indicated that IVIg, lamotrigine, muscle strengthening exercises and static magnetic fields may be beneficial but need further investigation to clarify whether any real and meaningful effect exists.
Topics: Cold Temperature; Exercise Therapy; Hot Temperature; Humans; Immunoglobulins, Intravenous; Lamotrigine; Muscle Fatigue; Muscle Strength; Postpoliomyelitis Syndrome; Randomized Controlled Trials as Topic; Triazines
PubMed: 25984923
DOI: 10.1002/14651858.CD007818.pub3 -
The Cochrane Database of Systematic... Jan 2008Although amantadine (AMT) and rimantadine (RMT) are used to relieve or treat influenza A symptoms in healthy adults, little is known about the effectiveness and safety... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although amantadine (AMT) and rimantadine (RMT) are used to relieve or treat influenza A symptoms in healthy adults, little is known about the effectiveness and safety of these antivirals in preventing and treating influenza A in children and the elderly.
OBJECTIVES
The aim of this review was to systematically consider evidence on the effectiveness and safety of AMT and RMT in preventing and treating influenza A in children and the elderly.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, issue 3); MEDLINE (1966 to July 2007) and EMBASE (1980 to July 2007).
SELECTION CRITERIA
Randomised or quasi-randomised trials comparing AMT and/or RMT in children and the elderly with placebo, control, other antivirals or comparing different doses or schedules of AMT and/or RMT or no intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and assessed methodological quality. Disagreements were resolved by consensus. In all comparisons except for one, the trials in children and in the elderly were analysed separately. Data were analysed and reported using Cochrane Review Manager 4.2. software.
MAIN RESULTS
In children, RMT was effective in the abatement of fever on day three of treatment. AMT showed a prophylactic effect against influenza A infection. AMT and RMT were not related to an increase in the occurrence of adverse effects. RMT also was considered to be well tolerated by the elderly, but showed no prophylactic effect. Different doses were comparable in the prophylaxis of influenza in the elderly, as well as in reporting adverse effects. Zanamivir prevented influenza A more effectively than RMT in the elderly.
AUTHORS' CONCLUSIONS
AMT was effective in the prophylaxis of influenza A in children. As confounding matters might have affected our findings, caution should be taken when considering which patients should to be given this prophylactic. Our conclusions about effectiveness of both antivirals for the treatment of influenza A in children were limited to a proven benefit of RMT in the abatement of fever on day three of treatment. Due to the small number of available studies we could not reach a definitive conclusion on the safety of AMT or the effectiveness of RMT in preventing influenza in children and the elderly.
Topics: Aged; Amantadine; Antiviral Agents; Child; Humans; Influenza A virus; Influenza, Human; Randomized Controlled Trials as Topic; Rimantadine; Sex Factors
PubMed: 18254006
DOI: 10.1002/14651858.CD002745.pub2 -
The Cochrane Database of Systematic... Apr 2006Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their potential value and... (Meta-Analysis)
Meta-Analysis 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 efficacy, effectiveness and safety ("effects") of amantadine and rimantadine in healthy adults.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to August Week 4, 2005), EMBASE (October 2003 to July 2005) and reference lists of articles.
SELECTION CRITERIA
Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control medication or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults.
DATA COLLECTION AND ANALYSIS
For prophylaxis (prevention) trials the numbers of participants with clinical influenza (influenza-like-illness or ILI) or with confirmed influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever, length of hospital stay and adverse effects.
MAIN RESULTS
Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.2). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prophylaxis 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. Neither drug affected the rate of viral shedding from the nose and the course of asymptomatic influenza.
AUTHORS' CONCLUSIONS
Amantadine and rimantadine have comparable efficacy and effectiveness in relieving or treating symptoms of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine. The effectiveness of both drugs in interrupting transmission is probably low. Routine use of both drugs should be discouraged and both drugs should only be used when all other measures fail.
Topics: Adult; Aged; Amantadine; Antiviral Agents; Drug Administration Schedule; Emergencies; Humans; Influenza A virus; Influenza, Human; Middle Aged; Randomized Controlled Trials as Topic; Rimantadine; Virus Shedding
PubMed: 16625539
DOI: 10.1002/14651858.CD001169.pub3 -
BMJ Clinical Evidence Mar 2009During the autumn-winter months (influenza seasons), influenza circulates more frequently, causing a greater proportion of influenza-like illness, and sometimes serious... (Review)
Review
INTRODUCTION
During the autumn-winter months (influenza seasons), influenza circulates more frequently, causing a greater proportion of influenza-like illness, and sometimes serious seasonal epidemics. The incidence of infection depends on the underlying immunity of the population.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of vaccines to prevent influenza? What are the effects of antiviral chemoprophylaxis of influenza? What are the effects of antiviral medications to treat influenza? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: vaccines, amantadine, oseltamivir, zanamivir, rimantadine.
Topics: Acute Disease; Administration, Inhalation; Humans; Incidence; Influenza Vaccines; Influenza, Human; Oseltamivir; Rimantadine; Zanamivir
PubMed: 19445759
DOI: No ID Found -
Health Technology Assessment... Feb 2009To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of... (Review)
Review
OBJECTIVES
To evaluate the clinical effectiveness and incremental cost-effectiveness of amantadine, oseltamivir and zanamivir for seasonal and post-exposure prophylaxis of influenza.
DATA SOURCES
A MEDLINE search strategy was used and searches were carried out in July 2007.
REVIEW METHODS
An independent health economic model was developed based on a review of existing cost-effectiveness models and clinical advice.The model draws together a broad spectrum of evidence relating to the costs and consequences associated with influenza and its prevention. Where direct evidence concerning the effectiveness of prophylaxis within specific model subgroups was lacking, the model uses estimates from mixed subgroups or extrapolates from other mutually exclusive subgroups.
RESULTS
Twenty-six published references relating to 22 randomised controlled trials (RCTs) were included in the clinical effectiveness review, along with one unpublished report. Eight, six and nine RCTs were included for amantadine, oseltamivir and zanamivir respectively. The study quality was variable and gaps in the evidence base limited the assessment of the clinical effectiveness of the interventions. For seasonal prophylaxis, there was limited evidence for the efficacy of amantadine in preventing symptomatic, laboratory-confirmed influenza (SLCI) in healthy adults [relative risk (RR) 0.40, 95% confidence interval (CI) 0.08-2.03]. Oseltamivir was effective in preventing SLCI, particularly when used in at-risk elderly subjects (RR 0.08, 95% CI 0.01-0.63). The preventative efficacy of zanamivir was most notable in at-risk adults and adolescents (RR 0.17, 95% CI 0.07-0.44), and healthy and at-risk elderly subjects (RR 0.20, 95% CI 0.02-1.72). For post-exposure prophylaxis, data on the use of amantadine were again limited: in adolescents an RR of 0.10 (95% CI 0.03-0.34) was reported for the prevention of SLCI. Oseltamivir was effective in households of mixed composition (RR 0.19, 95% CI 0.08-0.45). The efficacy of zanamivir in post-exposure prophylaxis within households was also reported (RR 0.21, 95% CI 0.13-0.33). Interventions appeared to be well tolerated. Limited evidence was available for the effectiveness of the interventions in preventing complications and hospitalisation and in minimising length of illness and time to return to normal activities. No clinical effectiveness data were identified for health-related quality of life or mortality outcomes. With the exception of at-risk children, the incremental cost-utility of seasonal influenza prophylaxis is expected to be in the range 38,000-428,000 pounds per QALY gained (depending on subgroup). The cost-effectiveness ratios for oseltamivir and zanamivir as post-exposure prophylaxis are expected to be below 30,000 pounds per QALY gained in healthy children, at-risk children, healthy elderly and at-risk elderly individuals. Despite favourable clinical efficacy estimates, the incorporation of recent evidence of viral resistance to amantadine led to it being dominated in every economic comparison.
CONCLUSIONS
All three interventions showed some efficacy for seasonal and post-exposure prophylaxis. However, weaknesses and gaps in the clinical evidence base are directly relevant to the interpretation of the health economic model and rendered the use of advanced statistical analyses inappropriate. These data limitations should be borne in mind in interpreting the findings of the review.
Topics: Amantadine; Antiviral Agents; Cost-Benefit Analysis; Humans; Influenza, Human; Models, Economic; Oseltamivir; Practice Guidelines as Topic; Premedication; Randomized Controlled Trials as Topic; Seasons; Treatment Outcome; Zanamivir
PubMed: 19215705
DOI: 10.3310/hta13110 -
Medicine Apr 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
OBJECTIVE
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
METHODS
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
RESULTS
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
CONCLUSION
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
Topics: Humans; Alzheimer Disease; Donepezil; Galantamine; Memantine; Molecular Docking Simulation; Cholinesterase Inhibitors; Rivastigmine
PubMed: 38640313
DOI: 10.1097/MD.0000000000037799 -
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 -
Neurodegenerative Disease Management Dec 2020Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but... (Meta-Analysis)
Meta-Analysis
Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but efficacy and safety remain unclear. We performed a systematic review and meta-analysis of qualified literatures searched until 30 April 2020. A total of 11 clinical trials were included. The meta-analysis revealed improvement of MS-related fatigue with amantadine treatment using the patients' subjective responses and validated fatigue scales. Amantadine is the most studied drug that has shown improvement of MS-related fatigue, with mild side effects and good tolerability. Larger studies using a standard measurement for MS-related fatigue are recommended to improve the quality of evidence. Safety and efficacy on long-term use needs further investigation.
Topics: Amantadine; Fatigue; Female; Humans; Male; Multiple Sclerosis
PubMed: 33012266
DOI: 10.2217/nmt-2020-0030