Monoamine oxidase B inhibitors versus other dopaminergic agents in early Parkinson's disease.
BACKGROUND
It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD) but trials have produced conflicting results.


OBJECTIVE
To assess the effectiveness and safety of long-term use of MAO-B inhibitors compared with other dopaminergic agents in early PD.


METHODS
We searched several electronic databases including: the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (January 1950 to February 2009) and EMBASE (January 1980 to February 2009). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers.


METHODS
We included all randomised controlled trials that compared a MAO-B inhibitor with other dopaminergic agents (presently levodopa or dopamine agonists) in patients with early PD, where treatment and follow up lasted at least one year.


METHODS
Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. Additional data were provided by the original authors. Random-effects models were used to analyse results, where appropriate.


RESULTS
Only two eligible trials were included (593 patients), both of reasonable quality although one was unblinded. Both trials compared selegiline with a dopamine agonist, whilst one also compared selegiline with levodopa. MAO-B inhibitors were not associated with a significant increase or decrease in deaths compared with levodopa (odds ratio (OR) 0.96; 95% confidence interval (CI) 0.52 to 1.76) or dopamine agonists (OR 1.30; 95% CI 0.69 to 2.45). Those receiving MAO-B inhibitors were more likely to require add-on therapy during follow-up than those receiving levodopa (OR 12.02; 95% CI 6.78 to 21.31) or dopamine agonist (OR 2.00; 95% CI 1.05 to 3.81). There was a reduction in motor fluctuations with MAO-B inhibitors compared with levodopa (OR 0.55; 95% CI 0.32 to 0.94) but not dopamine agonists (OR 1.15; 95% CI 0.65 to 2.05). Withdrawals due to adverse events were less common with MAO-B inhibitors than with dopamine agonists (OR 0.11; 95% CI 0.01 to 0.99).


CONCLUSIONS
MAO-B inhibitors are one option for the early treatment of PD although they have weaker symptomatic effects than levodopa and dopamine agonists. They may reduce the rate of motor fluctuations compared with initial levodopa therapy and may have fewer significant adverse effects than the older agonists but data are too few to provide reliable conclusions.
Caslake
Robert
R
Medecine & Therapeutics, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, UK, AB25 2ZD.
Macleod
Angus
A
Ives
Natalie
N
Stowe
Rebecca
R
Counsell
Carl
C
D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012642:Selegiline / Q000009:adverse effects / Q000627:therapeutic use
D018491:Dopamine Agonists; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D007980:Levodopa