In recent years, a few of randomized controlled trials (RCTs) about amantadine for treating dyskinesia in Parkinson's disease (PD) were completed. Here, we conducted a systematic literature review about the clinical research to provide the updated evidence for treating dyskinesia. Electronic search of Medline, PubMed, Cochrane Library, and other databases up to May 2016 for relevant studies was performed. We selected the Unified Parkinson's Disease Rating Scale IV (UPDRS IV) and Dyskinesia Rating Scales (DRS) as efficacy outcomes of amantadine on dyskinesia. Pooled data from included studies was then used to carry out meta-analysis. A total of eleven eligible RCTs that involved 356 PD patients with existing dyskinesia were included in the present study. The results of meta-analysis showed that amantadine significantly improved UPDRS IV (P < 0.0001) and DRS (P < 0.00001). Meanwhile, there was a mild reduction in Unified Parkinson's Disease Rating Scale III after amantadine treatment in advanced PD patients with dyskinesia (P = 0.01) compared with placebo. High dosage of amantadine obviously improved existing dyskinesia in PD, yet at the expense of the increased adverse events. It was necessary to detect the optimal therapeutic efficacy to balance the incidence of adverse events when we used amantadine to treat existing dyskinesia in PD patients.
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.
OBJECTIVE: To evaluate the effectiveness and safety of amantadine in Parkinson’s disease.
METHODS: Cochrane library, Pubmed database, Embase database, ISI database, CBM database, CNKI database, VIP database, Articles Database in computer were searched. Randomized controlled trials (RCT), systematic review (SR) or Meta analysis of amantadine vs placebo in Parkinson´s disease were selected, then quality evaluation and Meta-analysis were performed. The conclusions of the included SR and Metaanalysis
were taken into consideration.
RESULTS: There were 9 RCTs of amantadine vs placebo in treating parkinson´s disease. The result showed that the efficacy of amantadine was better than placebo [RR 0. 14, 95% CI (0. 06, 0. 29), P ＜ 0. 000 01]. Amantadine was better than placebo to improve parkinson's symptoms [RR － 3. 21, 95% CI (－ 5. 88－ 0. 54), P = 0. 02]. When it comes to ADR, there was no significant difference between amantadine and placebo
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.
AUTHORS' 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.
In recent years, a few of randomized controlled trials (RCTs) about amantadine for treating dyskinesia in Parkinson's disease (PD) were completed. Here, we conducted a systematic literature review about the clinical research to provide the updated evidence for treating dyskinesia. Electronic search of Medline, PubMed, Cochrane Library, and other databases up to May 2016 for relevant studies was performed. We selected the Unified Parkinson's Disease Rating Scale IV (UPDRS IV) and Dyskinesia Rating Scales (DRS) as efficacy outcomes of amantadine on dyskinesia. Pooled data from included studies was then used to carry out meta-analysis. A total of eleven eligible RCTs that involved 356 PD patients with existing dyskinesia were included in the present study. The results of meta-analysis showed that amantadine significantly improved UPDRS IV (P < 0.0001) and DRS (P < 0.00001). Meanwhile, there was a mild reduction in Unified Parkinson's Disease Rating Scale III after amantadine treatment in advanced PD patients with dyskinesia (P = 0.01) compared with placebo. High dosage of amantadine obviously improved existing dyskinesia in PD, yet at the expense of the increased adverse events. It was necessary to detect the optimal therapeutic efficacy to balance the incidence of adverse events when we used amantadine to treat existing dyskinesia in PD patients.
Systematic Review Question»Systematic review of interventions
