Levetiracetam for levodopa-induced dyskinesia in Parkinson's disease: a randomized, double-blind, placebo-controlled trial

The aim of this study was to assess the efficacy, safety and tolerability of the antiepileptic compound levetiracetam (LEV) for the treatment of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). We thus performed a randomized, double-blind, placebo-controlled, parallel-group pilot study in PD patients with moderate-to-severe LID on stable dopaminergic therapy. Placebo or LEV was administered twice daily (titrated from 250 to 2,000 mg/day) as add-on therapy. Subjects underwent evaluation of the unified-PD-rating scale (UPDRS) and the modified abnormal involuntary movement scale (AIMS). The primary outcome variable was the change of the AIMS score between baseline and end-of-treatment visit. Secondary variables included total UPDRS score and response to levodopa challenge. Of 32 randomized patients (mean age 65.2 years, 62.5% women), 17 received LEV and 15 placebo. After 11 weeks of treatment, mean changes of the modified AIMS from baseline were -1.5 (-26%) for LEV (p = 0.332) and +0.9 (+13%) for placebo (p = 0.588) without significant differences between groups. Mean changes of the UPDRS item 32/33 sum score from baseline showed significant improvement of dyskinesia in the LEV group [-1.0 (-20%); p = 0.012], but not in the placebo group [-0.4 (-8%); p = 0.306]. Treatment had no effects on UPDRS motor score or levodopa response. Frequency and quality of adverse events were similar in both treatment groups. Together, LEV showed only mild antidyskinetic effects without worsening of Parkinsonian symptoms or compromising levodopa efficacy. LEV was well tolerated in doses up to 2,000 mg/day. Further large controlled studies are warranted to evaluate the impact of LEV on LID in PD patients.