Comparative effectiveness of dopamine agonists and monoamine oxidase type-B inhibitors for Parkinson's disease: a multiple treatment comparison meta-analysis


Abstract

Purpose: To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson''s disease.

Methods: We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson''s disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson''s Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.

Results: Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.

Conclusions: Dopamine agonists were found to be effective as treatment for Parkinson''s disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson''s disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.

Keywords: Dopamine agonists; Effectiveness; MAO-B inhibitors; Multiple treatment comparison; Parkinson’s disease; Serious adverse events.

Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

Fig.?1
Fig.?1
Identification and selection of publications. MAO-B inhibitors included and adapted from [4]
Fig.?2
Fig.?2
Overview of direct and indirect comparisons. The numbers and the thickness of the lines indicate the number of clinical trials in each comparison
Fig.?3
Fig.?3
Histograms displaying a given dopamine agonist or MAO-B inhibitor’s effect ranked against the other drugs (ranked from left to right) when given as monotherapy. The height of the bars gives the probability of being ranked as number one to seven. The effect ratios are the estimated effect of given drug versus placebo treatment. ROP, ropinirole; LD, levodopa; PRA, pramipexole; ROT, rotigotine; SE, selegiline; RA, rasagiline; CAB, cabergoline
Fig.?4
Fig.?4
Histograms displaying given dopamine agonist or MAO-B inhibitor’s effect ranked against the other drugs (ranked from left to right) when given in combination with levodopa. The height of the bars gives the probability of being ranked as number one to seven. The effect rations are the estimated effect of the given drug versus placebo treatment when given in combination with levodopa. SE, selegiline; PRA, pramipexole; ROP, ropinirole; ROT, rotigotine; CAB, cabergoline; RA, rasagiline; SA, safinamide
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