BACKGROUND: Dyskinesia is a motor complication of Parkinson's disease (PD) posing therapeutic challenges. The optimal therapy for dyskinesia in PD has not been identified due to the lack of comprehensive evaluation of treatments. OBJECTIVE: The aim was to compare the efficacy and safety of interventions for alleviating levodopa-induced dyskinesia in PD. METHODS: We conducted a Bayesian network meta-analysis (NMA) by systematically searching PubMed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, and EudraCT databases up to April 1, 2024. The primary efficacy outcome was the change in scores on dyskinesia rating scales from baseline. RESULTS: The study included 85 randomized controlled trials (RCT) involving 13,826 PD patients, comprising 39 interventions. Nine treatments were significantly more effective in reducing scores on dyskinesia rating scales than control (placebo, sham surgery, sham repetitive transcranial magnetic stimulation, or best medical treatment). Globus pallidus interna deep brain stimulation (GPi-DBS) had the highest probability to be the most effective (standardized mean difference, 95% credible interval: -1.27, -1.65 to -0.88
surface under the cumulative ranking curve [SUCRA]: 97.4%), followed by levodopa-carbidopa intestinal gel infusion (SUCRA = 89.7%), subthalamic nucleus (STN)-DBS (SUCRA = 89%), immediate-release (IR) amantadine (SUCRA = 86.5%), pallidotomy (SUCRA = 84.9%), ADS-5102 (SUCRA = 82.9%), clozapine (SUCRA = 77.2%), OS320 (SUCRA = 64.8%), and AFQ056 (SUCRA = 54.5%). GPi-DBS was superior to STN-DBS, and pallidotomy ranked higher than subthalamotomy. ADS-5102 and OS320 had higher adverse event (AE) rates compared to control, whereas AFQ056 and ADS-5102 were linked to more serious AEs. CONCLUSIONS: This RCT-based NMA identifies and ranks nine efficacious interventions for dyskinesia in PD. GPi-DBS may be the most effective therapy for treating dyskinesia, with IR amantadine ranking highest among oral medications. Novel anti-dyskinetic medications are associated with less-favorable tolerance profiles. © 2025 International Parkinson and Movement Disorder Society.