OBJECTIVE: To define key issues in the management of Parkinson disease (PD) relating to neuroprotective strategies and alternative treatments, and to make evidence-based treatment recommendations.
METHODS: Two clinical questions were identified. 1) In a patient diagnosed with PD, are there any therapies that can slow disease progression? 2) Are there any nonstandard pharmacologic or nonpharmacologic therapies that have been shown to improve motor function in PD? Articles were classified according to a four-tiered level of evidence scheme. Recommendations were based on the evidence.
RESULTS AND CONCLUSIONS: 1. Levodopa does not appear to accelerate disease progression. 2. No treatment has been shown to be neuroprotective. 3. There is no evidence that vitamin or food additives can improve motor function in PD. 4. Exercise may be helpful in improving motor function. 5. Speech therapy may be helpful in improving speech volume. 6. No manual therapy has been shown to be helpful in the treatment of motor symptoms, although studies in this area are limited. Further studies using a rigorous scientific method are needed to determine efficacy of alternative therapies.
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.
We evaluated the efficacy of physiotherapy, occupational therapy, and speech and language therapy in Parkinson's disease by synthesizing six Cochrane systematic reviews. All randomised, controlled trials examining the efficacy of a paramedical therapy versus control intervention and all those comparing the efficacy of two forms of active therapy in Parkinson's disease were included. Trials were identified by searching biomedical databases, reference lists, hand searching, and contacting investigators. The main outcome measures were quality of life, speech intelligibility, activities of daily living, and individual measures of motor and speech impairment. We identified 16 physiotherapy randomised controlled trials (399 patients), two occupational therapy trials (84 patients), and five speech and language therapy for dysarthria trials (154 patients). None of these studies examined nonpharmacological swallowing therapy for dysphagia. We were unable to perform meta-analysis of the results because the trials used heterogeneous therapy methods and outcome measures. The trials also had marked methodological flaws that could have introduced bias. In summary, we failed to find conclusive evidence of benefit for any form of paramedical therapy sufficient to recommend them in routine clinical practice. However, this lack of evidence is not proof of a lack of effect. Further large pragmatic randomised controlled trials are required to determine the effectiveness of paramedical therapies in Parkinson's disease.
Epidemiological research has confirmed that Parkinson's disease (PD) is found throughout the world and increases exponentially with age. Few good-quality data on the temporal incidence of PD are available, although both mortality and incidence data suggest that the disease may be less common today in younger age groups. Differences in prevalence between identical ethnic groups in different countries support the role of an environmental factor. Any postulated factor must be found commonly in developed countries, among which there appears to be little difference in incidence or prevalence rates. A wide variety of aetiological agents have been considered from infectious, toxic and other exposures. The most robust finding is that non-smokers have a greater risk of disease, although the reason for this is unclear and may relate to differences in pre-morbid personality. Pesticides and head injuries also show consistently elevated risk but are prone to biased measurement. Dietary anti-oxidants require further evaluation. Future research needs to improve on current limited methods of exposure measurement and to attempt more novel designs to overcome bias. More attention should be made on examining what factors determine prognosis and using epidemiological and qualitative methods to determine the needs of patients with PD.
To define key issues in the management of Parkinson disease (PD) relating to neuroprotective strategies and alternative treatments, and to make evidence-based treatment recommendations.
METHODS:
Two clinical questions were identified. 1) In a patient diagnosed with PD, are there any therapies that can slow disease progression? 2) Are there any nonstandard pharmacologic or nonpharmacologic therapies that have been shown to improve motor function in PD? Articles were classified according to a four-tiered level of evidence scheme. Recommendations were based on the evidence.
RESULTS AND CONCLUSIONS:
1. Levodopa does not appear to accelerate disease progression. 2. No treatment has been shown to be neuroprotective. 3. There is no evidence that vitamin or food additives can improve motor function in PD. 4. Exercise may be helpful in improving motor function. 5. Speech therapy may be helpful in improving speech volume. 6. No manual therapy has been shown to be helpful in the treatment of motor symptoms, although studies in this area are limited. Further studies using a rigorous scientific method are needed to determine efficacy of alternative therapies.
