Parkinson’s disease is a gradually progressive neurodegenerative disease with symptoms such as rest tremor, rigidity and bradykinesia. Many patients also experience depression, sleep issues and cognitive impairment. Parkinson’s disease affects 0.3% of the entire population in industrialized countries.

There is no cure for Parkinson’s disease, and hence all treatment is symptomatic. Treatment with levodopa, dopamine agonists (DA) and monoamine oxidase type-B inhibitors (MAO-B) (rasagline, selegine, safinamide) are given alone or in combinations. All these drugs increase the neurotransmitter dopamine in the brain.

We conducted a literature search identifying 27 published studies on randomized controlled trials assessing the efficacy of MAO-B inhibitors in adult patients with Parkinson’s disease. From these studies we identified three networks of drug comparisons, see the figure below.

For each of these networks we considered a joint model for assessing the comparable relative effects between the various MAO-B inhibitors and the comparator drug. We also considered the occurrence of serious adverse events (SAE). We estimated the relative effect of each MAO-B inhibitor versus placebo (network 1), versus placebo + levodopa (network 2) and placebo + dopamine agonists (network 3). We took into consideration disease duration and dose level.

We found that all MAO-B inhibitors were effective when compared to placebo, both when given as monotherapy and in combination with levodopa. When given alone we found no significant difference between the MAO-Bs, but when given with levodopa we found that selegine was the most effective drug. We did not find any MAO-B inhibitor to be better or worse with respect to SAE.

A large randomized controlled trial comparing all available treatments, reporting data on the patient level, would be a gold standard, but often no such trial exists. This work demonstrates the importance of comparative analyses, and their ability to add valuable information to treatment guidelines.

Figure: RA= rasagline, SA= safinamide, SE= selegine, LD=levodopa, DA= dopamine agonists, P=placebo, EN= entacapone (a catechol-O-methyltransferase inhibitor also sometimes used together with levodopa for treating Parkinson’s disease). The numbers indicate the number of comparisons between drugs.

Binde, Caroline Ditlev; Tvete, Ingunn Fride; Gåsemyr, Jørund Inge; Natvig, Bent & Klemp, Marianne (2018). A multiple treatment comparison meta-analysis of monoamine oxidase type B inhibitors for Parkinson's disease. British Journal of Clinical Pharmacology.  ISSN 0306-5251.  84(9), s 1917- 1927 . doi: 10.1111/bcp.13651: