Objective: To review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine agonists (DAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson’s disease (PD) experiencing motor complications.
Background: When PD progresses motor complications can occur. To optimize dopaminergic therapy COMT-Is, DAs or MAOB-Is are often prescribed in addition to levodopa. To date, guidelines do not state a preference for one of the three drug classes.
Method: In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomized controlled trials (RCTs) between 1980-2021. RCTs were included if either a COMT-I, DA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor fluctuations and dyskinesia. The main outcomes included daily off-medication time and adverse events including dyskinesia. For comparisons with placebo, we calculated the efficacy and safety outcomes using the random effects model. For direct comparisons across therapies, network meta-analyses with a Bayesian hierarchical random effects model were used.
Results: 74 RCTs reporting on 18,693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean 0.8 hours (95%CI 1.0 to 0.6), DAs -1.1 hours (95%CI -1.4 to 0.8), MAOB-Is -0.9 hours (95%CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DAs 3.0 (95%CI 2.5 to 3.5), MAOB-Is 1.6 (95%CI 1.2 to 2.2)). According to the surface under the cumulative ranking curve (SUCRA) scores, pramipexol IR was associated with the most favorable benefit-risk profile.
[Figure 1]
Conclusion: COMT-Is, DAs and MAOB-Is effectively reduce motor fluctuations and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DAs appeared most effective.
To cite this abstract in AMA style:
V. Sisodia, L. Dubbeld, RMA. de Bie, GS. Duarte, J. Costa, JM. Dijk. Efficacy and safety of adjunctive oral therapy in Parkinson’s disease with motor complications: a systematic review and network meta-analysis [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-adjunctive-oral-therapy-in-parkinsons-disease-with-motor-complications-a-systematic-review-and-network-meta-analysis/. Accessed June 15, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-and-safety-of-adjunctive-oral-therapy-in-parkinsons-disease-with-motor-complications-a-systematic-review-and-network-meta-analysis/