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Therapeutic Advances in Rare Disease 2022The rare inherited autosomal recessive disease Friedreich ataxia (FA) causes progressive neurodegenerative changes and disability in patients. A systematic literature... (Review)
Review
OBJECTIVES
The rare inherited autosomal recessive disease Friedreich ataxia (FA) causes progressive neurodegenerative changes and disability in patients. A systematic literature review (SLR) was carried out to understand and summarize the published efficacy and safety of therapeutic interventions in this disease.
METHODS
Database searches were carried out in MEDLINE, Embase, and Cochrane by two independent reviewers. In addition, trial registries and conference proceedings were hand-searched.
RESULTS
Thirty-two publications were deemed eligible according to PICOS criteria. Twenty-four publications detail randomized controlled trials. The most frequently identified therapeutic intervention was idebenone ( = 11), followed by recombinant erythropoietin ( = 6), omaveloxolone ( = 3), and amantadine hydrochloride ( = 2). Other therapeutic interventions were investigated in one publication: A0001, CoQ10, creatine, deferiprone, interferon-γ-1b, the L-carnitine levorotatory form of 5-hydroxytryptophan, luvadaxistat, resveratrol, RT001, and vatiquinone (EPI-743). These studies included patients from 8 to 73 years old, and disease duration varied from 4.7 to 19 years. Disease severity as per the mean GAA1 and GAA2 allele repeat length ranged from 350 to 930 and 620 to 987 nucleotides, respectively. Most frequently reported efficacy outcomes were the International Cooperative Ataxia Rating Scale (ICARS, = 10), the Friedreich Ataxia Rating Scale (modified FARS and FARS-neuro, = 12), the Scale for Assessment and Rating of Ataxia (SARA, = 7), and the Activities of Daily Living scale (ADL, = 8). Each of these assesses the severity of disability in FA patients. In many studies, patients with FA deteriorated according to these severity scales regardless of treatment, or inconclusive results were found. Generally, these therapeutic interventions were well-tolerated and safe. Serious adverse events were atrial fibrillation ( = 1), craniocerebral injury ( = 1), and ventricular tachycardia ( = 1).
CONCLUSION
Identified literature showed a considerable unmet need for therapeutic interventions that halt or slow the deteriorating nature of FA. Novel efficacious drugs should be investigated that aim to improve symptoms or slow disease progression.
PubMed: 37180421
DOI: 10.1177/26330040221139872 -
The Cochrane Database of Systematic... Mar 2013Influenza is a communicable acute respiratory infection which, during epidemics, can cause high morbidity and mortality rates. Traditional Chinese medicinal herbs, often... (Review)
Review
BACKGROUND
Influenza is a communicable acute respiratory infection which, during epidemics, can cause high morbidity and mortality rates. Traditional Chinese medicinal herbs, often administered following a particular Chinese medical theory, may be a potential treatment of choice.
OBJECTIVES
To assess the effect of Chinese medicinal herbs used to prevent and treat influenza and to estimate the frequency of adverse effects.
SEARCH METHODS
We searched CENTRAL (2012, Issue 11), MEDLINE (January 1966 to November week 2, 2012), EMBASE (January 1988 to November 2012) and CNKI (January 1988 to 29 March 2012). We also searched reference lists of articles and the WHO ICTRP search portal (November 2012).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing traditional Chinese medicinal herbs with placebo, no treatment or conventional medicine normally used in preventing and treating uncomplicated influenza.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality.
MAIN RESULTS
We included 18 studies involving 2521 participants. The methodological quality of 17 included studies was poor. Included RCTs separately compared medicinal herbs with different antiviral drugs, precluding any pooling of results. Only three indicated that compared with antiviral drugs, Chinese medicinal herbs may be effective in preventing influenza and alleviating influenza symptoms. 'Ganmao' capsules were found to be more effective than amantadine in decreasing influenza symptoms and speeding recovery in one study (in which adverse reactions were mentioned in the amantadine group although no data were reported). There were no significant differences between 'E Shu You' and ribavirin in treating influenza, nor in the occurrence of adverse reactions. Ten studies reported mild adverse reactions.
AUTHORS' CONCLUSIONS
Most Chinese medical herbs in the included studies showed similar effects to antiviral drugs in preventing or treating influenza. Few were shown to be superior to antiviral drugs. No obvious adverse events were reported in the included studies. However, current evidence remains weak due to methodological limitations of the trials. More high-quality RCTs with larger numbers of participants and clear reporting are needed.
Topics: Amantadine; Antiviral Agents; Drugs, Chinese Herbal; Humans; Influenza, Human; Phytotherapy; Randomized Controlled Trials as Topic; Ribavirin
PubMed: 23543533
DOI: 10.1002/14651858.CD004559.pub4 -
Parkinson's Disease 2019Since the discovery of levodopa (L-dopa) in 1967, the range of medications available to treat Parkinson's disease has increased significantly and guidance on the use,... (Review)
Review
Since the discovery of levodopa (L-dopa) in 1967, the range of medications available to treat Parkinson's disease has increased significantly and guidance on the use, efficacy, and safety of these medications has evolved. To assess levels of adherence to national prescribing guidelines and awareness of changes in the efficacy and safety data published in the profiles of medications for the treatment of PD, we have reviewed studies on patterns and determinants of prescribing PD medications conducted in the last 50 years (since the discovery of L-dopa). A systematic literature review was conducted using EMBASE (1967 to March, 2018), Ovid MEDLINE(R) ALL (1967 to March 16, 2018), PsycINFO (1967 to the 2 week of March, 2018), and PubMed to identify all studies measuring prescribing patterns of PD medication between 1967 and 2017. Study design, source of data, country, year of study, number of patients and/or prescriptions, unit of analysis, prescribing determinants, and percentage utilisation of PD medications were extracted where possible. 44 studies examining prescribing patterns and/or prescribing determinants across 17 countries were identified. Unsurprisingly, L-dopa was the most commonly prescribed medication in all studies, accounting for 46.50% to 100% of all prescriptions for PD. In several studies, the prescribing rate of ergot-derived dopamine agonists (DAs) decreased over time in concordance with guidance. In contrast, the prescribing rates of non-ergot DAs increased over the last ten years in most of the included studies. In examining prescribing factors, two major categories were exemplified, patients' factors and prescribers' factors, with patients' age being the most common factor that affected the prescription in most studies. In conclusion, L-dopa is now the most commonly prescribed medication for cases of PD but there is large variation in the prescribing rates of catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, amantadine, and anticholinergics between countries. New studies examining the effects of recent clinical trials and measuring the prescribing rates of newly approved medications are warranted.
PubMed: 31781365
DOI: 10.1155/2019/9237181 -
Brain & Spine 2024TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on... (Review)
Review
INTRODUCTION
TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness. It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition. The current study will synthesize the current available evidence and show the effect of Amantadine in functional improvement after TBI.
RESEARCH QUESTION
Does Amantadine have an effect on functional improvement of TBI patients?
MATERIAL AND METHODS
This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores.
RESULTS
Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores.
DISCUSSION AND CONCLUSION
Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.
PubMed: 38465280
DOI: 10.1016/j.bas.2024.102773 -
The Cochrane Database of Systematic... Feb 2021Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of... (Review)
Review
BACKGROUND
Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug - cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine - are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment.
OBJECTIVES
To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer-related outcomes.
SEARCH METHODS
We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources.
SELECTION CRITERIA
We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed citations and full-text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3-11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods.
MAIN RESULTS
We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias. Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) -0.42, 95% confidence interval (CI) -0.64 to -0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD -0.40, 95% CI -0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD -0.62; 95% CI -0.94 to -0.31). Data from one longer-term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) -2.09 Standardised Mini-Mental State Examination (SMMSE) points, 95% CI -3.43 to -0.75; moderate certainty). Discontinuation may make little or no difference to functional status in the short term (SMD -0.25, 95% CI -0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD -0.38, 95% CI -0.74 to -0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD -3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI -6.67 to -0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD - 0.48, 95% CI -0.82 to -0.13; 2 studies; low certainty; and SMD -0.27, 95% CI -0.47 to -0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD -0.87 Neuropsychiatric Inventory (NPI) points; 95% CI -8.42 to 6.68; moderate certainty). We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review.
AUTHORS' CONCLUSIONS
This review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well-designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.
Topics: Activities of Daily Living; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Memantine; Parkinson Disease; Quality of Life; Rivastigmine
PubMed: 35608903
DOI: 10.1002/14651858.CD009081.pub2 -
The Cochrane Database of Systematic... Nov 2022Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of... (Review)
Review
BACKGROUND
Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.
SEARCH METHODS
For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022.
SELECTION CRITERIA
We included randomised controlled (RCTs) trials that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled.
MAIN RESULTS
Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated "prevention" of cognitive problems (during radiotherapy and follow-up) and four studies investigated "amelioration" (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the "early radiotherapy treatment phase" were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the "early radiotherapy treatment phase" included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme. In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The "amelioration" pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had "stable" brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias.
AUTHORS' CONCLUSIONS
In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.
Topics: Adult; Humans; Modafinil; Donepezil; Memantine; Quality of Life; Cognitive Dysfunction; Cranial Irradiation; Cognition; Methylphenidate; Brain Neoplasms; Fatigue; Dementia
PubMed: 36427235
DOI: 10.1002/14651858.CD011335.pub3 -
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... Jan 2007Fatigue is one of the most common and disabling symptoms of people with Multiple Sclerosis (MS). The effective management of fatigue has an important impact on the... (Review)
Review
BACKGROUND
Fatigue is one of the most common and disabling symptoms of people with Multiple Sclerosis (MS). The effective management of fatigue has an important impact on the patient's functioning, abilities, and quality of life. Although a number of strategies have been devised for reducing fatigue, treatment recommendations are based on a limited amount of scientific evidence. Many textbooks report amantadine as a first-choice drug for MS-related fatigue because of published randomised controlled trials (RCTs) showing some benefit.
OBJECTIVES
To determine the effectiveness and safety of amantadine in treating fatigue in people with MS.
SEARCH STRATEGY
We searched The Cochrane MS Group Trials Register (July 2006), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2006), MEDLINE (January 1966 to July 2006), EMBASE (January 1974 to July 2006), bibliographies of relevant articles and handsearched relevant journals. We also contacted drug companies and researchers in the field.
SELECTION CRITERIA
Randomised, placebo or other drugs-controlled, double-blind trials of amantadine in MS people with fatigue.
DATA COLLECTION AND ANALYSIS
Three reviewers selected studies for inclusion in the review and they extracted the data reported in the original articles. We requested missing and unclear data by correspondence with the trial's principal investigator. A meta-analysis was not performed due to the inadequacy of available data and heterogeneity of outcome measures.
MAIN RESULTS
Out of 13 pertinent publications, 5 trials met the criteria for inclusion in this review: one study was a parallel arms study, and 4 were crossover trials. The number of randomised participants ranged between 10 and 115, and a total of 272 MS patients were studied. Overall the quality of the studies considered was poor and all trials were open to bias. All studies reported small and inconsistent improvements in fatigue, whereas the clinical relevance of these findings and the impact on patient's functioning and health related quality of life remained undetermined. The number of participants reporting side effects during amantadine therapy ranged from 10% to 57%.
AUTHORS' CONCLUSIONS
The efficacy of amantadine in reducing fatigue in people with MS is poorly documented, as well as its tolerability. It is advisable to: (1) improve knowledge on the underlying mechanisms of MS-related fatigue; (2) achieve anagreement on accurate, reliable and responsive outcome measures of fatigue; (3) perform good quality RCTs.
Topics: Amantadine; Antiviral Agents; Cross-Over Studies; Dopamine Agents; Fatigue; Humans; Multiple Sclerosis; Randomized Controlled Trials as Topic
PubMed: 17253480
DOI: 10.1002/14651858.CD002818.pub2 -
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... May 2015Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development.
OBJECTIVES
To investigate the efficacy and acceptability of dopamine agonists alone or in combination with any psychosocial intervention for the treatment of of people who misuse cocaine.
SEARCH METHODS
We run the search on 12 January 2015. We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, CINAHL, PsycINFO, ICTRP, clinicaltrials.gov and screened reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing dopamine agonists alone or associated with psychosocial intervention with placebo, no treatment or other pharmacological interventions.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
Twenty four studies, including 2147 participants, met the inclusion criteria. Comparing any dopamine agonist versus placebo, we found no differences for any of the outcomes considered: dropout (moderate quality of evidence), abstinence (low quality of evidence), severity of dependence (low quality of evidence), adverse events (moderate quality of evidence). This was also observed when single dopamine agonists were compared against placebo. Comparing amantadine versus antidepressants, we found low quality of evidence that antidepressants performed better for abstinence (RR 0.25, 95% CI 0.12 to 0.53) based on two studies with 44 participants. No differences were found for dropout or adverse events, for both moderate quality of evidence.The major flaws of the included studies concerned selection bias because most studies did not report information about sequence generation (80%) and allocation concealment methods (86%): half of the included studies were judged at unclear risk of performance bias and 62.5% at unclear risk of detection bias for what concerns subjective outcomes.
AUTHORS' CONCLUSIONS
Current evidence from RCTs does not support the use of dopamine agonists for treating cocaine misuse. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment. Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention, which was suggested by the previous Cochrane Review (Soares 2003), is not supported by the results of this Cochrane Review update.
Topics: Amantadine; Antidepressive Agents; Bromocriptine; Cocaine-Related Disorders; Depression; Dopamine Agonists; Humans; Levodopa; Randomized Controlled Trials as Topic; Selection Bias
PubMed: 26014366
DOI: 10.1002/14651858.CD003352.pub4