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The Cochrane Database of Systematic... Dec 2014Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy.
OBJECTIVES
To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy.
SEARCH METHODS
On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies.
SELECTION CRITERIA
We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials.
MAIN RESULTS
The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving a favourable outcome six weeks post-intervention (odds ratio (OR) 0.56 (95% confidence interval (CI) 0.22 to 1.35, N = 74, P = 0.16). We assessed the quality of this evidence as low. Two parallel-group randomised double-blind, placebo-controlled trials comparing the effects of two doses of ascorbic acid with placebo for reducing fatigue in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) showed that the effects of ascorbic acid at either dose are probably small (standardised mean difference (SMD) -0.12 (95% CI -0.32 to 0.08, n = 404, P = 0.25)) for change in fatigue after 12 to 24 months (moderate quality evidence). Neither ascorbic acid study measured fatigue at four to 12 weeks, which was our primary outcome measure. No serious adverse events were reported with amantadine. Serious adverse events were reported in the trials of ascorbic acid. However,risk of serious adverse events was similar with ascorbic acid and placebo.
AUTHORS' CONCLUSIONS
One small imprecise study in people with GBS showed uncertain effects of amantadine on fatigue. In two studies in people with CMT1A there is moderate-quality evidence that ascorbic acid has little meaningful benefit on fatigue. Information about adverse effects was limited, although both treatments appear to be well tolerated and safe in these conditions.There was no evidence available from RCTs to evaluate the effect of other drugs or other interventions for fatigue in either GBS, CMT1A or other causes of peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future randomised clinical trials.
Topics: Adult; Amantadine; Ascorbic Acid; Charcot-Marie-Tooth Disease; Child; Fatigue; Guillain-Barre Syndrome; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic
PubMed: 25519471
DOI: 10.1002/14651858.CD008146.pub2 -
Contemporary Clinical Trials May 2022COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors...
The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.
BACKGROUND
COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications.
METHODS AND RESULTS
The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine.
CONCLUSIONS
Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome.
CLINICAL TRIAL REGISTRATION
www.
CLINICALTRIALS
gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).
Topics: Amantadine; COVID-19; Humans; Respiratory Insufficiency; SARS-CoV-2; Treatment Outcome; Post-Acute COVID-19 Syndrome; COVID-19 Drug Treatment
PubMed: 35390511
DOI: 10.1016/j.cct.2022.106755 -
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 -
BMJ Open Jan 2024Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although...
Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial.
INTRODUCTION
Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.
METHODS AND ANALYSIS
The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5-4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12-18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.
ETHICS AND DISSEMINATION
The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.
TRIAL REGISTRATION NUMBER
EudraCT 2021-004868-95; NCT05809414.
Topics: Adult; Humans; Multiple Sclerosis; Transcranial Magnetic Stimulation; Quality of Life; Amantadine; Double-Blind Method; Fatigue; Treatment Outcome; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 38176857
DOI: 10.1136/bmjopen-2023-078661 -
International Journal of Molecular... Jul 2022Patients with Parkinson’s disease are prone to a higher incidence of melanoma. Amantadine (an anti-Parkinson drug) possesses the antiproliferative potential that can...
Patients with Parkinson’s disease are prone to a higher incidence of melanoma. Amantadine (an anti-Parkinson drug) possesses the antiproliferative potential that can be favorable when combined with other chemotherapeutics. Cisplatin (CDDP) and mitoxantrone (MTO) are drugs used in melanoma chemotherapy, but they have many side effects. (1) Clinical observations revealed a high incidence of malignant melanoma in patients with Parkinson’s disease. Amantadine as an anti-Parkinson drug alleviates symptoms of Parkinson’s disease and theoretically, it should have anti-melanoma properties. (2) To characterize the interaction profile for combinations of amantadine with CDDP and MTO in four human melanoma cell lines (A375, SK-MEL 28, FM55P and FM55M2), type I isobolographic analysis was used in the MTT test. (3) Amantadine produces the anti-proliferative effects in various melanoma cell lines. Flow cytometry analysis indicated that amantadine induced apoptosis and G1/S phase cell cycle arrest. Western blotting analysis showed that amantadine markedly decreased cyclin-D1 protein levels and increased p21 levels. Additionally, amantadine significantly increased the Bax/Bcl-2 ratio. The combined application of amantadine with CDDP at the fixed-ratio of 1:1 exerted an additive interaction in the four studied cell lines in the MTT test. In contrast, the combination of amantadine with MTO (ratio of 1:1) produced synergistic interaction in the FM55M2 cell line in the MTT (* p < 0.05). The combination of amantadine with MTO was also additive in the remaining tested cell lines (A375, FM55P and SK-MEL28) in the MTT test. (4) Amantadine combined with MTO exerted the most desirable synergistic interaction, as assessed isobolographically. Additionally, the exposure of melanoma cell lines to amantadine in combination with CDDP or MTO augmented the induction of apoptosis mediated by amantadine alone.
Topics: Amantadine; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cisplatin; Cytostatic Agents; Humans; Melanoma; Parkinson Disease
PubMed: 35886997
DOI: 10.3390/ijms23147653 -
Journal of Enzyme Inhibition and... Dec 2023An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation...
An important drug used in the treatment of Parkinson's disease is amantadine. We are the first to perform a comprehensive study based on various glycation and oxidation factors, determining the impact of amantadine on protein glycoxidation. Sugars (glucose, fructose, galactose) and aldehydes (glyoxal, methylglyoxal) were used as glycation agents, and chloramine T was used as an oxidant. Glycoxidation biomarkers in albumin treated with amantadine were generally not different from the control group (glycation/oxidation factors), indicating that the drug did not affect oxidation and glycation processes. Molecular docking analysis did not reveal strong binding sites of amantadine on the bovine serum albumin structure. Although amantadine poorly scavenged hydroxyl radical and hydrogen peroxide, it had significantly lower antioxidant and antiglycation effect than all protein oxidation and glycation inhibitors. In some cases, amantadine even demonstrated glycoxidant, proglycation, and prooxidant properties. In summary, amantadine exhibited weak antioxidant properties and a lack of antiglycation activity.
Topics: Antioxidants; Glycation End Products, Advanced; Molecular Docking Simulation; Serum Albumin, Bovine; Amantadine
PubMed: 36325591
DOI: 10.1080/14756366.2022.2137161 -
The Journal of Head Trauma...To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to...
Prescribing Patterns of Amantadine During Pediatric Inpatient Rehabilitation After Traumatic Brain Injury: A Multicentered Retrospective Review From the Pediatric Brain Injury Consortium.
OBJECTIVES
To describe dosing practices for amantadine hydrochloride and related adverse effects among children and young adults with traumatic brain injury (TBI) admitted to pediatric inpatient rehabilitation units.
SETTING
Eight pediatric acute inpatient rehabilitation units located throughout the United States comprising the Pediatric Brain Injury Consortium.
PARTICIPANTS
Two-hundred thirty-four children and young adults aged 2 months to 21 years with TBI.
DESIGN
Retrospective data revie.
MAIN OUTCOME MEASURES
Demographic variables associated with the use of amantadine, amantadine dose, and reported adverse effects.
RESULTS
Forty-nine patients (21%) aged 0.9 to 20 years received amantadine during inpatient rehabilitation. Forty-five percent of patients admitted to inpatient rehabilitation with a disorder of consciousness (DoC) were treated with amantadine, while 14% of children admitted with higher levels of functioning received amantadine. Children with DoC who were not treated with amantadine were younger than those with DoC who received amantadine (median 3.0 vs 11.6 years, P = .008). Recorded doses of amantadine ranged from 0.7 to 13.5 mg/kg/d; the highest total daily dose was 400 mg/d. Adverse effects were reported in 8 patients (16%); nausea/abdominal discomfort and agitation were most common, each reported in 3 patients. The highest reported dose without an adverse effect was 10.1 mg/kg/d.
CONCLUSION
During pediatric inpatient rehabilitation, amantadine was prescribed to children across a range of ages and injury severity and was most commonly prescribed to older children with DoC. Dosing varied widely, with weight-based dosing for younger/smaller children at both lower and higher doses than what had been previously reported. Prospective studies are needed to characterize the safety and tolerability of higher amantadine doses and optimize amantadine dosing parameters for children with TBI.
Topics: Adolescent; Amantadine; Brain Injuries; Brain Injuries, Traumatic; Child; Humans; Inpatients; Retrospective Studies; United States; Young Adult
PubMed: 34320554
DOI: 10.1097/HTR.0000000000000709 -
Journal of Molecular Medicine (Berlin,... May 2018Amantadine has been shown to reduce anesthesia and surgery-induced neuroinflammation and cognitive dysfunction. It is known that sepsis can impair brain function. We...
UNLABELLED
Amantadine has been shown to reduce anesthesia and surgery-induced neuroinflammation and cognitive dysfunction. It is known that sepsis can impair brain function. We determined whether amantadine-attenuated sepsis-induced neuroinflammation and dysfunction of learning and memory and whether toll-like receptors (TLRs) play a role in the effects. Six- to eight-week-old mice were subjected to cecal ligation and puncture (CLP). Amantadine at 30 mg/kg/day was injected intraperitoneally for 3 days. CU-CPT22, a TLR1/TLR2 inhibitor, at 3 mg/kg/day was injected intraperitoneally for 2 days. Mice were subjected to Barnes maze and fear conditioning tests from 1 week after CLP. CLP induced neuroinflammation and cognitive dysfunction. CLP also increased the expression of toll-like receptor 2 (TLR2), TLR4, and TLR9, three major TLRs in the brain, in CD-1 male mice. Amantadine attenuated CLP-induced neuroinflammation and dysfunction of learning and memory but did not have significant effects on the expression of TLRs. CU-CPT22 also attenuated sepsis-induced neuroinflammation and cognitive dysfunction. Similarly, sepsis induced neuroinflammation and cognitive dysfunction in the C57BL/6J mice. Interestingly, sepsis also induced neuroinflammation and cognitive dysfunction in the TLR2 knockout mice. The effects of amantadine on the neuroinflammation and cognitive dysfunction were still apparent in these knockout mice. TLR2 contributes to sepsis-induced neuroinflammation and cognitive dysfunction. However, inhibiting TLR2 may not be a major mechanism for amantadine to inhibit sepsis-induced neuroinflammation and cognitive dysfunction.
KEY MESSAGES
Sepsis induces neuroinflammation and cognitive impairment, which were attenuated by amantadine. Toll-like receptors 2 mediates these sepsis effects but may not be the major target for amantadine to reduce these effects.
Topics: Amantadine; Animals; Behavior, Animal; Cognitive Dysfunction; Hippocampus; Male; Maze Learning; Mice, Inbred C57BL; Mice, Knockout; Neuroprotective Agents; Sepsis; Toll-Like Receptors
PubMed: 29502203
DOI: 10.1007/s00109-018-1631-z -
Cleveland Clinic Journal of Medicine Jan 2012Most, if not all, currently available drugs for Parkinson disease address dopaminergic loss and relieve symptoms. However, their adverse effects can be limiting and they... (Review)
Review
Most, if not all, currently available drugs for Parkinson disease address dopaminergic loss and relieve symptoms. However, their adverse effects can be limiting and they do not address disease progression. Moreover, nonmotor features of Parkinson disease such as depression, dementia, and psychosis are now recognized as important and disabling. A cure remains elusive. However, promising interventions and agents are emerging. As an example, people who exercise regularly are less likely to develop Parkinson disease, and if they develop it, they tend to have slower progression.
Topics: Age Factors; Amantadine; Antiparkinson Agents; Apomorphine; Catechol O-Methyltransferase; Cholinergic Antagonists; Disease Progression; Dopamine Agents; Humans; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 22219231
DOI: 10.3949/ccjm.78gr.11005 -
Viruses Oct 2021We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In...
We report the in vitro efficacy of ion-channel inhibitors amantadine, memantine and rimantadine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In VeroE6 cells, rimantadine was most potent followed by memantine and amantadine (50% effective concentrations: 36, 80 and 116 µM, respectively). Rimantadine also showed the highest selectivity index, followed by amantadine and memantine (17.3, 12.2 and 7.6, respectively). Similar results were observed in human hepatoma Huh7.5 and lung carcinoma A549-hACE2 cells. Inhibitors interacted in a similar antagonistic manner with remdesivir and had a similar barrier to viral escape. Rimantadine acted mainly at the viral post-entry level and partially at the viral entry level. Based on these results, rimantadine showed the most promise for treatment of SARS-CoV-2.
Topics: A549 Cells; Adenosine Monophosphate; Alanine; Amantadine; Animals; Antiviral Agents; Cell Line, Tumor; Chlorocebus aethiops; Denmark; Drug Repositioning; Humans; Ion Channels; Memantine; Rimantadine; SARS-CoV-2; Vero Cells; COVID-19 Drug Treatment
PubMed: 34696509
DOI: 10.3390/v13102082