Abstract
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 methods
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.
Plain language summary
There is not enough evidence about the safety and effectiveness of amantadine for people with dyskinesia in Parkinson’s disease.
Levodopa is regarded as the most effective treatment for Parkinson’s disease but in many patients it causes abnormal involuntary movements known as dyskinesias. It is thought that amantadine may be added to levodopa to reduce dyskinesias in patients with Parkinson’s disease without worsening Parkinsonian symptoms. This review found that there is not enough evidence from trials about the effects of amantadine for people with dyskinesia in Parkinson’s disease. Adverse effects in trials so far have included confusion, worsening of hallucinations, the re-emergence of palpitations, nausea, dry mouth, swelling of feet and constipation.
