Buspirone and Zolmitriptan Combination for Dyskinesia: A Randomized, Controlled, Crossover Study

Abstract Background Preclinical evidence suggests that co‐administration of the 5‐HT 1A agonist buspirone and the 5‐HT 1B/1D agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone. Objectives Assess the therapeutic potential of a fixed‐dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa‐induced dyskinesia. Methods Single‐center, randomized, placebo‐controlled, two‐way crossover study (NCT02439203) of a fixed‐dose buspirone/zolmitriptan regimen (10/1.25 mg three times a day) in 30 patients with PD experiencing at least moderately disabling peak‐effect dyskinesia. Results Seven days of treatment with buspirone/zolmitriptan added to levodopa significantly reduced dyskinesia as assessed by Abnormal Involuntary Movement Scale scores versus placebo (mean treatment effect vs. placebo: −4.2 [−6.1, −2.3]) without significantly worsening Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON) scores (mean treatment effect vs. placebo: 0.6 [−0.1, 1.3]). No serious adverse events were reported. Conclusions In this proof‐of‐concept study, addition of buspirone/zolmitriptan to the patients’ PD medication regimen significantly reduced dyskinesia severity without worsening motor function. © 2024 International Parkinson and Movement Disorder Society.