scholarly journals N-Methyl-D-Aspartate Antagonists in Levodopa Induced Dyskinesia: A Meta-Analysis

2012 ◽  
Vol 39 (4) ◽  
pp. 465-472 ◽  
Author(s):  
Behzad Elahi ◽  
Nicolás Phielipp ◽  
Robert Chen
Keyword(s):  
Clinical Trials ◽  
Nmda Receptor ◽  
Rating Scales ◽  
Rating Scale ◽  
Meta Analysis ◽  
Nmda Receptor Antagonists ◽  
Controlled Clinical Trials ◽  
Receptor Antagonists ◽  
Peak Dose ◽  
Standard Mean Difference

Background:Levodopa-induced dyskinesias (LID) are amongst the most disabling side-effects of levodopa therapy for Parkinson's disease (PD). It has been suggested that that N-Methyl-D-Aspartate (NMDA)-receptor antagonist may reduce peak-dose dyskinesia in PD patients and may lead to motor improvement. In this study, we compared the efficacy of NMDA receptor antagonists versus placebo in the treatment of LID in PD through a meta-analysis of controlled trials.Methods:Electronic search of Pubmed (1990 - 2010), Medline (1966-2010), EMBASE (1974-2010) and other databases for relevant studies were performed. Controlled clinical trials of the effects of NMDA antagonists on LID that fulfill the study protocol were selected. Pooled data from included studies was then used to perform random and fixed effect models meta-analysis.Results:The search resulted in 11 randomized, placebo controlled clinical trials that involved a total of 253 PD patients with peak-dose LID. The outcome measures were various dyskinesia rating scales and the Unified Parkinson Disease Rating Scale (UPDRS) subscales III and IV. The analysis showed significant reduction in Standard Mean Difference (SMD) for UPDRS IV (SMD -1.45; 95% CI -2.28 to -0.63) and UPDRS III (SMD -0.41; 95% CI -0.69 to -0.12) after treatment with amantadine. Other included drugs did not show significant change in the outcomes measured.Conclusion:This meta-analysis provides an update on the clinical trials and confirms the short-term benefits of amantadine therapy in the treatment of dyskinesia. The effects of other NMDA receptor antagonists need to be evaluated further in clinical trials.

Meta-analysis of Placebo-controlled Clinical Trials of Safinamide and Entacapone as Add-on Therapy to Levodopa in the Treatment of Parkinson’s Disease

2015 ◽  
Vol 10 (01) ◽  
pp. 15 ◽  
Author(s):  
Jörg Schnitker ◽  
Thomas Müller ◽  
◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Rating Scale ◽  
Meta Analysis ◽  
Search Term ◽  
Motor Complications ◽  
Controlled Clinical Trials ◽  
Total Incidence ◽  
Double Blinded

Chronic levodopa (L-dopa) treatment of Parkinson’s disease (PD) patients is sooner or later associated with the onset of motor complications, for example wearing off and dyskinesia. PD patients with motor complications usually require the addition of further PD drugs to reduce these L-dopa side effects and enhance its efficacy. Entacapone is an available catechol-O-methyltransferase (COMT) inhibitor, which was extensively investigated as add-on to L-dopa/dopadecarboxylase inhibitor (DDCI) application in PD patients. Safinamide, a watersoluble, orally active a-aminoamide derivative, which modulates dopaminergic and glutamatergic neurotransmission with a unique dual mechanism of action, has been studied in two placebo-controlled clinical trials as add-on therapy to L-dopa in fluctuating PD patients. To date, there are no head-to-head clinical trials comparing the efficacy of safinamide and entacapone in the clinic. The aim of this meta-analysis was to determine effect sizes of safinamide and entacapone as add-on treatment to L-dopa in fluctuating PD patients. A systematic search of the literature on entacapone trials up to the end of September 2014 was first conducted on the MEDLINE and EMBASE databases in order to identify appropriate studies. Definition criteria for inclusion were prospective, randomised, placebocontrolled and double-blinded trials on the efficacy and safety of entacapone or safinamide in fluctuating L-dopa-treated PD patients. Four studies for entacapone and two trials on safinamide were considered. Data from the safinamide trials were provided by Zambon and therefore ‘safinamide’ was not used as a search term. Safinamide and entacapone treatment was comparable in terms of the main efficacy variables (offtime, percentageontime, Unified Parkinson’s Disease Rating Scale). Significant advantages in favour of safinamide were shown in terms of the total incidence of adverse events (AEs) in comparison to placebo, the study discontinuation due to AEs and deaths and in the risk differences of the AEs versus placebo, particularly for nausea, vomiting, diarrhoea, dizziness, urine abnormality and shortness of breath. The odds ratio (OR) of 0.907 for any AE corresponds to an overall AE rate of 68.7 % for safinamide whereas the OR of 2.089 to an overall AE rate of 84.4 % for entacapone.

scholarly journals Intranasal Application of Xenon Reduces Opioid Requirement and Postoperative Pain in Patients Undergoing Major Abdominal Surgery

2011 ◽  
Vol 115 (2) ◽  
pp. 398-407 ◽  
Author(s):  
Thorsten Frederik Holsträter ◽  
Michael Georgieff ◽  
Karl Josef Föhr ◽  
Werner Klingler ◽  
Miriam Elisabeth Uhl ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Postoperative Pain ◽  
Central Sensitization ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Study ◽  
Opioid Tolerance ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Intranasal Application

Background Both central sensitization after peripheral tissue injury and the development of opioid tolerance involve activation of N-methyl-D-aspartate (NMDA) receptors. At subanesthetic doses the NMDA receptor antagonist xenon suppresses pain-evoked sensitization of pain-processing areas in the central nervous system. Although numerous studies describe the effect of NMDA receptor antagonists on postoperative pain, clinical studies elucidating their intraoperative analgesic potency when applied in a low dosage are still largely missing. Methods To analyze the analgesic effect of low-dose xenon using new application methods, the authors tested nasally applied xenon as an add-on treatment for analgesia in 40 patients undergoing abdominal hysterectomy. Within a randomized double-blind placebo-controlled study design, intraoperative and postoperative requirement of opioids as well as postoperative subjective experiences of pain were measured as primary outcome variables. Results Intranasal application of xenon significantly reduced intraoperative opioid requirement (mean difference [MD] -2.0 μg/min; 95% CI [CI95]-0.53 to -3.51, Bonferroni correction adjusted P value [pcorr]= 0.028) without relevant side effects and significantly reduced postoperative pain (MD -1.34 points on an 11-point rating scale; CI95 -0.60 to -2.09, pcorr = 0.002). However, postoperative morphine consumption (MD -8.8 μg/min; CI95 1.2 to -18.8, pcorr = 0.24) was not significantly reduced in this study. Conclusions Low-dose xenon significantly reduces intraoperative analgesic use and postoperative pain perception. Because NMDA receptor antagonists suppress central sensitization, prevent the development of opioid tolerance, and reduce postoperative pain, the intraoperative usage of NMDA receptor antagonists such as xenon is suggested to improve effectiveness of pain management within a concept of multimodal analgesia.

scholarly journals NMDA receptor antagonists in the treatment of neurological diseases

2020 ◽  
Vol 12 (5) ◽  
pp. 71-77
Author(s):  
I. S. Preobrazhenskaya
Keyword(s):  
Clinical Trials ◽  
Nmda Receptor ◽  
Clinical Case ◽  
Neurological Diseases ◽  
Cognitive Impairments ◽  
Cognitive Disorders ◽  
Nmda Receptor Antagonists ◽  
Fetal Alcohol ◽  
Receptor Antagonists ◽  
Neurodegenerative Dementias

The paper reviews clinical trials evaluating the efficacy of N-methyl-D-aspartate (NMDA) receptor antagonists used to treat various neurological diseases: neurodegenerative dementias, vascular cognitive disorders, including post-stroke cognitive impairment. It discusses the possibility of treating cognitive disorders with NMDA receptor antagonists in Parkinson's disease, traumatic brain injury, and some other diseases, as well as the potential possibilities of using drugs of this pharmacotherapeutic group in childhood. The paper describes a clinical case illustrating the use of akatinol memantine in a child with a delay in speech and mental development in the presence of fetal alcohol syndrome. The possibilities of using akatinol memantine in the treatment of childhood cognitive impairments are sure to be of particular interest; however, in view of the small amount of data, this aspect requires further clinical trials.

scholarly journals ANTI-INFLAMMATORIES FOR DELAYED ONSET MUSCLE SORENESS: SYSTEMATIC REVIEW AND META-ANALYSIS

2021 ◽  
Vol 27 (6) ◽  
pp. 646-654
Author(s):  
Roberto Lohn Nahon ◽  
Jaqueline Santos Silva Lopes ◽  
Anibal Monteiro de Magalhães Neto ◽  
Aloa de Souza Machado ◽  
Luiz Claudio Cameron
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Muscle Soreness ◽  
Meta Analysis ◽  
Delayed Onset Muscle Soreness ◽  
Significant Heterogeneity ◽  
Cochrane Central Register ◽  
Controlled Clinical Trials ◽  
Delayed Onset ◽  
Standard Mean Difference

ABSTRACT Objective: To investigate the effectiveness of pharmacological interventions in the treatment of delayed onset muscle soreness (DOMS). Design: A systematic review and meta-analysis of randomized controlled clinical trials (RCTs). Data sources: The PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs published prior to August 3, 2020. Eligibility criteria for selecting studies: Studies that 1) used an RCT design; 2) evaluated the effectiveness of steroidal or nonsteroidal anti-inflammatory drugs (NSAIDs) in treating DOMS; and 3) therapeutically used drugs after exercise were included. Results: In total, 26 studies (patients = 934) were eligible for inclusion in the qualitative analysis on the treatment of DOMS. The results of the meta-analysis showed no superiority between the use and non-use of NSAIDs in the improvement of late muscle pain, as no statistically significant differences were verified (21 studies, n= 955; standard mean difference (SMD)= 0.02; 95% confidence interval (CI) −0.58, 0.63; p=0.94; I2=93%). The quality of the synthesized evidence was very low according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and there was significant heterogeneity among the included studies. Conclusion: The results demonstrate that NSAIDs are not superior to controls/placebos in treating DOMS. The inclusion of both studies with dose-response protocols and those with exercise protocols may have influenced the results. In addition, the high risk of bias identified reveals that limitations need to be considered when interpreting the results. Level of evidence I; ystematic review of RCT (Randomized and Controlled Clinical Trials).

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