Efficacy and safety of perampanel in Parkinson’s disease. A systematic review with meta-analysis

Simona Lattanzi, Elisabetta Grillo, Francesco Brigo, Mauro Silvestrini

L-Dopa represents the mainstay of therapy of Parkinson's disease (PD), but its effectiveness is reduced with continued treatment and disease progression. Accordingly, there remains a need to explore novel treatment strategies to manage the signs and symptoms of the later disease stages. The aim of the study was to evaluate the efficacy and safety of adjunctive perampanel (PER) in patients with PD through a meta-analysis of existing trials. Randomized, placebo-controlled, double- or single-blind, add-on studies of PER in patients with PD were identified through a systematic literature search. The following outcomes were assessed: changes from baseline to final efficacy visit in total daily OFF time, activities of daily living during OFF time and motor function during ON time, incidence of adverse events (AEs), and treatment withdrawal. Four trials were included involving 2266 participants, 1449 and 817 for PER and placebo treatment groups, respectively. Four PER daily doses were tested, namely 0.5, 1, 2 and 4 mg. There were no significant differences in any efficacy outcome between PER and placebo treated patients. The risk ratios (RRs) for AEs, severe AEs and treatment withdrawal were similar between placebo and PER at 0.5, 1 and 2 mg; the 4 mg daily dose was associated with an increased risk of AEs [RR 1.118 (1.047-1.193)], and withdrawal for AEs [RR 1.345 (1.034-1.749)] and for any reason [RR 1.197 (1.020-1.406)]. In PD patients experiencing motor fluctuations, adjunctive PER did not improve the motor state and was well-tolerated at the lower doses.