N-Methyl-D-Aspartate antagonists in levodopa induced dyskinesia: a meta-analysis.
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.


CONCLUSIONS
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.
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Behzad
B
Elahi
Nicolás
N
Phielipp
Robert
R
Chen
D000547:Amantadine / Q000627:therapeutic use; D016208:Databases, Factual / Q000706:statistics & numerical data; D004185:Disability Evaluation; D004311:Double-Blind Method; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000517:prevention & control*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D000547:Amantadine