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Monoamine oxidase B inhibitors versus other dopaminergic agents in early Parkinson's disease

  • Review
  • Intervention

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Abstract

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.

Objectives

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

Search 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.

Selection criteria

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.

Data collection and analysis

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.

Main 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).

Authors' 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.

Plain language summary

Monoamine oxidase B inhibitors compared with other treatments in early Parkinson's

Many of the symptoms of Parkinson's disease are due to the loss of certain groups of nerves in the brain, which results in the lack of a chemical called dopamine. Currently, there are several different treatments available for people with newly diagnosed Parkinson's including levodopa (Sinemet or Madopar) which is converted into dopamine in the brain, dopamine agonists (for example, ropinirole and pramipexole) which mimic the action of dopamine, and monoamine oxidase B (MAO-B) inhibitors (selegiline or rasagiline) which reduce the breakdown of dopamine in the brain. Each of these types of drugs has theoretical advantages and disadvantages. For example, although a very good treatment, levodopa can cause involuntary movements (dyskinesia), painful cramps (dystonia) and a shortened response to each dose (motor fluctuations) after a while, whilst MAO-B inhibitors and dopamine agonists may reduce the risk of these complications but are not so good at improving the symptoms of Parkinson's. At present, therefore, it is not clear which of these three groups of drugs should be prescribed when people with early Parkinson's first need treatment. We reviewed the trials that compared giving MAO-B inhibitors with other types of medication in people with early Parkinson's to see if there was good evidence that MAO-B inhibitors were the best treatment to offer. However, unfortunately we only identified two trials (593 patients) so there was only limited evidence. The results showed that MAO-B inhibitors were less good at improving the symptoms of Parkinson's than either levodopa or dopamine agonists but that they may reduce motor fluctuations compared with levodopa, though not compared with dopamine agonists. MAO-B inhibitors did, however, have fewer major side effects than some dopamine agonists.

Laički sažetak

Inhibitori monoaminooksidaze B u usporedbi s drugim terapijama u ranoj fazi Parkinsonove bolesti

Mnogi od simptoma Parkinsonove bolesti nastaju zbog gubitka pojedinih skupina živaca u mozgu, što dovodi do kemijskog nedostatka kemijskog spoja koji se naziva dopamin. Trenutno postoji nekoliko različitih terapija na raspolaganju za osobe s tek dijagnosticiranom Parkinsonovom bolesti, uključujući levodopu (Sinemet ili Madopar) koji se konvertira u dopamin u mozgu, agoniste dopamina (na primjer, ropinirol i pramipeksol) koji oponašaju djelovanje dopamina te inhibitore monoamin oksidaze B (MAO-B) (selegilin i razagilin), koji smanjuju razgradnju dopamina u mozgu. Svaka od tih vrsta lijekova ima svoje teoretske prednosti i nedostatke. Na primjer, iako je vrlo dobar način liječenja, levodopa može uzrokovati nehotične pokrete (diskinezija), bolne grčeve (distonija) i skraćene reakcije na svaku dozu (motoričke fluktuacije) nakon nekog vremena, dok istovremeno inhibitori MAO-B i agonisti dopamina mogu smanjiti rizik tih komplikacija, ali nisu toliko dobri u poboljšanju simptoma Parkinsonove bolesti. Dakle, trenutno nije jasno koju od tih triju skupina lijekova treba propisati prilikom početka liječenja oboljelih od Parkinsonove bolesti. U ovom Cochrane sustavnom pregledu analizirana je literatura kako bi se pronašla istraživanja koja su uspoređivala korištenje inhibitora MAO-B s drugim vrstama lijekova u osoba s ranom Parkinsonovom bolesti da bi se pronašli dokazi da li su inhibitori MAO-B najbolja terapija koja se može ponuditi. No, nažalost, pronađena su samo dva istraživanja (593 bolesnika), tako da su dokazi ograničeni. Rezultati pokazuju da su inhibitori MAO-B manje uspješni u poboljšanju simptoma Parkinsonove bolesti u odnosu na levodopu ili agoniste dopamina, ali da mogu smanjiti motoričke fluktuacije u usporedbi s levodopom, iako ne i u usporedbi s agonistima dopamina. Međutim, inhibitori MAO-B imaju manje nuspojava od nekih agonista dopamina.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Diana Rubić
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

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