Objective: To investigate the efficacy of buspirone on levodopa induced dyskinesias (LID) in Parkinson disease (PD) patients

Background: LID could be partially mediated by the metabolism of levodopa in serotoninergic neurons. In open-label studies, buspirone has improved LID but might also worsen parkinsonian symptoms

Method: We designed a Phase 3 multicentric randomized placebo-controlled trial to measure the efficacy of buspirone to reduce LID in PD patients. Patients were selected according to the following criteria: dyskinesia during at least 25% of the day; stable dose of dopaminergic treatment during the 4 weeks preceding selection; Hoehn & Yahr ≤3 (On) and ≤4 (Off); MMSE ≥24. Patients already treated by amantadine or subthalamic nucleus deep-brain stimulation (DBS) could be included. Buspirone was escalated to reach 10 mg 3 times daily at week 4 and continued until week 12. Dose could be reduced in case of intolerance. The primary objective was the change in the UDysRS score at Week 12 compared to baseline.

Results: A total of 99 patients (mean age 66 y. [59-71] were randomized to placebo (n=51) or buspirone (n=48). Among them, 11 had DBS and 54 were treated by amantadine (placebo n=30; buspirone n=24). At baseline, the mean [range] MDS-UPDRS motor scores (on) were 19.5 [12.8, 35.6] in the placebo group and 22.5 [15.0, 33.8] in the buspirone group.

The average dose of buspirone reached by the patient was 17.2 ± 9.9 mg. Changes in the scores from baseline to 12 weeks remained non-significant between the placebo and buspirone groups and were respectively: UDysRS -5.5 [-19, +4] vs. -8.0 [-12,-3]; PDQ-39 -5.5 [-19.3, +4.0] vs. -4.0 [-11.5, +4.0]; Epworth 0 [-3, +2] vs. -1.5 [-5, +1]. Score of depression (Hamilton scale) did not change over the 12 weeks. Worsening of parkinsonian (increased off time, falls) symptoms was observed in 16/51 patients with placebo vs. 17/48 patients with buspirone and worsening of LID was observed in 8/51 patients with placebo and 11/48 patients with buspirone.

Conclusion: Compared to placebo, buspirone fails to improve significantly LID in PD patients. No significant worsening of PD symptoms nor daily sleepiness was observed in the buspirone group. The lack of benefit could be due to an insufficient dose of buspirone or the lack of additional benefit in combination with amantadine, which reduced the power of the study.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multicentric-randomized-control-trial-of-buspirone-in-levodopa-induced-dyskinesias/