Treatment of restless legs syndrome with the selective AMPA receptor antagonist perampanel

Perampanel is a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) antagonist that has been approved for the treatment of partial seizures. Here we report on the first open study evaluating its efficacy in idiopathic restless legs syndrome (RLS).The study was designed as a prospective two-month open trial. Twenty-two previously untreated patients diagnosed with idiopathic RLS began treatment with 2 mg perampanel, which was increased to 4 mg at week four if clinically necessary. Multiple Suggested Immobilization Tests (mSITs) followed by polysomnography were performed at baseline and at week eight. Severity ratings were performed every two weeks by means of the IRLS scale, and Clinical Global Index (CGI) subscale. The main endpoint was therapeutic response, defined as a 50% improvement in IRLS total score.Twenty patients completed the study. During the 8-week treatment period, the IRLS score improved from a mean (±standard deviation (SD)) 23.7 ± 4.2 to 11.5 ± 5.3. Twelve of 20 patients were full responders (improvement 50% in IRLS total score), and four responded partially. The mean effective dose of perampanel at the end of treatment was 3.8 mg/day. Treatment with perampanel also resulted in an improvement in the mean (±SD) periodic leg movement index from 27.8 ± 6.9 to 4.36 ± 2.0. Perampanel was well tolerated. The main side effects were dizziness, somnolence, headache, and irritability.These preliminary results suggest that perampanel has significant therapeutic effects on both sensory and motor symptoms. If confirmed by future controlled studies, perampanel might become a promising alternative to existing dopaminergic treatments due to its glutamatergic mechanism of action. The study provides class IV evidence supporting the therapeutic effects of perampanel in RLS/WED.