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.

Drug selection and timing of initiation of treatment in early Parkinson's disease

“…The clinical benefit of selegiline is relatively mild, with most studies showing a total UPDRS improvement of 2.7 points at 3 months. 70 In a long-term follow-up study of the DATATOP cohort, L-dopa-treated patients who were originally randomized to selegiline had significantly less decline, with less wearing off, on-off, and freezing episodes. 71 Similar benefits of early selegiline treatment together with re-duced L-dopa dose requirements were observed in the long-term Nordic study.…”

Has drug therapy changed the natural history of Parkinson’s disease?

“…A systematic review of monoamine oxidase B inhibitor symptomatic therapy trials [12] showed a similar positive effect of an initial policy of MAOBI therapy with a reduction in motor fluctuations of 25% (Fig. 7).…”

A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson’s disease models

“…Consequently, PD patients are mainly diagnosed based on symptoms, with neuroimaging tests such as the DA-based PET imaging being used for confirmation, although its high cost precludes its routine use in the clinic 47 . No cure for PD is presently available; however, several MAO-B inhibitors have been shown to provide relief from the symptoms and are currently being used for the treatment of early-stage PD [11][12][13] . The biological and clinical importance of MAO-B in PD has led us to successfully develop U1, a first-generation, two-photon fluorogenic imaging probe.…”

“…In PD patients, the elevation in MAO-B activity causes highly membrane-permeable H 2 O 2 generated to diffuse from astrocytes to neighbouring neuronal cells, which consequently leads to oxidative stress and their eventual degeneration. Notably, both selegiline and rasagiline are FDAapproved drugs for the treatment of early-stage PD, and they work by selectively inhibiting overexpressed MAO-B activity in the patients [11][12][13] . MAO-A-selective inhibitors such as clorgyline, however, are devoid of such therapeutic effects.…”