Objective: To evaluate the efficacy of buspirone in combination with amantadine in reducing levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease (PD).

Background: LID is an undesirable adverse effect of chronic levodopa (LD) therapy in PD. Approximately half of the patients required medication adjustment or additional medications to manage LID[1]. The increasing utilization of deep brain stimulation for the treatment of LID indicates that best medical management is not enough. Use 5-HT1A agonists as a method of blocking LID in the rat model has opened a door for alternative treatment strategies in humans. Bonifati et al. (1994) found that monotherapy of buspirone 20mg daily had significant reduction in LID (5/7 subjects)[2]. While amantadine is effective at reducing LID, clinical practice has shown that the benefits of the drug are eventually overcome by progression of disease. When a disease becomes refractory to monotherapy adding an adjuvant medication often yields good results.

Method: A randomized, placebo-controlled, double-blind, two-period cross-over study to evaluate the efficacy of a novel treatment combination (amantadine and buspirone) for LID in PD. Each phase titrates study drug (amantadine + placebo or amantadine + buspirone) for two weeks ending in 30 mg/day. Participants complete LID, tremor, and PD ratings during a day-long outpatient visit with 1.5x clinical oral LD dose. Each phase is followed by a 7±5 day washout.

Results: To date, 5 subjects have been enrolled and randomized. One subject withdrew prior to initiating study drug due to difficulties in travelling to the VA for the day-long study visit. All participants were Caucasian non-Hispanic (3 male/1 female). All participants met the United Kingdom Brain Bank criteria for PD. See table 1 for baseline characteristics and figure 1 for an example of the blinded data for one subject over both phases. Analysis is on-going.

Conclusion: With the advanced understanding of the mechanisms by which LID likely occurs, we can now consider adopting the rational polypharmacy approach to its management.

References: [1]. Müller T, Woitalla D, Russ H, Hock K, Haeger DA. Prevalence and treatment strategies of dyskinesia in patients with Parkinson’s disease. Journal of Neural Transmission. 2007;114(8):1023-6. [2]. Bonifati V, Fabrizio E, Cipriani R, Vanacore N, Meco G. Buspirone in levodopa-induced dyskinesias. Clin Neuropharmacol. 1994 Feb;17(1):73-82.

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