Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients

Abstract

Objective: To quantify more reliably the benefits and risks of monoamine oxidase type B inhibitors (MAOBIs) in early Parkinson's disease.

Data sources: Searches of the Cochrane Library, Medline, Embase, PubMed, and Web of Science for years 1966-2003, plus major journals in the field, abstract books, and proceedings of meetings, for randomised trials comparing MAOBIs with placebo or levodopa.

Data extraction: Available data on mortality, motor complications, side effects, treatment compliance, and clinician rated disability (for example, unified Parkinson's disease rating scale) were extracted from 17 trials and combined using standard meta-analytic methods.

Results: No significant difference in mortality existed between patients on MAOBIs and control patients (odds ratio 1.13, 95% confidence interval 0.94 to 1.34; P = 0.2). Patients randomised to MAOBIs had significantly better total scores, motor scores, and activities of daily living scores on the unified Parkinson's disease rating scale at three months compared with patients taking placebo; they were also less likely to need additional levodopa (0.57, 0.48 to 0.67; P < 0.00001) or to develop motor fluctuations (0.75, 0.59 to 0.95; P = 0.02). No difference existed between the two groups in the incidence of side effects or withdrawal of patients.

Conclusions: MAOBIs reduce disability, the need for levodopa, and the incidence of motor fluctuations, without substantial side effects or increased mortality. However, because few trials have compared MAOBIs with other antiparkinsonian drugs, uncertainty remains about the relative benefits and risks of MAOBIs. Further large, long term comparative trials that include patient rated quality of life measures are needed.

Fig 1

Mortality in trials of monoamine oxidase type B inhibitors. (LD=levodopa; MAOBI=monoamine oxidase type B inhibitor; O-E=observed minus expected; RR=re-randomisation data from UK-PDRG. ^*Data from subsequent follow up of UK-PDRG trial—patients counted only once in total denominator)

Fig 2

Need for levodopa treatment in trials comparing monoamine oxidase type B inhibitors and placebo. (O-E=observed minus expected; LD=levodopa; MAOBI=monoamine oxidase type B inhibitor. ^*Rasagiline. †O-E and variance based on published time to event analyses)

Fig 3

Incidence of motor complications in trials of monoamine oxidase type B inhibitors. (O-E=observed minus expected; LD=levodopa; MAOBI=monoamine oxidase type B inhibitor. ^*Motor fluctuations defined as on-off or end of dose fluctuations, wearing off, or random oscillations)

Fig 4

Withdrawal of patients due to adverse events in trials of monoamine oxidase type B inhibitors (O-E=observed minus expected; LD=levodopa; MAOBI=monoamine oxidase type B inhibitor)