Persistence of Effect of Dextromethorphan Hydrobromide/Quinidine Sulfate (DM/Q) for Pseudobulbar Affect (PBA): Results from a 12-Week Open-Label Extension (OLE) Study (P6.313)

Objective: To evaluate persistence of effect for DM/Q in PBA treatment. Background: PBA results from neurologic injury and is characterized by sudden, involuntary outbursts of laughing and/or crying. DM/Q 20/10 mg twice daily remains the only treatment FDA-approved for PBA. Design/Methods: 12-week, OLE for patients with PBA secondary to amyotrophic lateral sclerosis or multiple sclerosis completing a 12-week, double-blind (DB), phase 3 trial (NCT00573443). Patients entered the OLE within 14 days of the last DB dose. DB treatment arms included placebo, DM/Q 20/10 mg, or DM/Q 30/10 mg twice daily; during OLE, patients received DM/Q 30/10 mg twice daily. Center for Neurologic Study-Lability Scale (CNS-LS) scores were measured at all clinic visits and allowed ad hoc evaluation of persistence of efficacy. Results: Of 253 enrolled OLE patients, 92.9% completed and 4% discontinued for adverse events. Regardless of DB treatment assignment, PBA symptoms significantly improved from DB baseline (CNS-LS mean score [SD] of 20.4[4.8]) throughout the OLE. Mean CNS-LS changes from DB baseline to each OLE visit (OLE Days 15[n=245], 42[n=241], and 84[n=237]) were −9.4[5.5], −9.3[5.5], and −9.2[5.6], respectively (all P 48-hour gap in DM/Q treatment between DB and OLE had a significant return of PBA symptoms while off treatment (mean[SD] CNS-LS increase=4.5[5.2]; P Conclusions: DM/Q showed persistent efficacy in treating PBA throughout 24 weeks of DB and OLE treatment. Patients with a greater than 2-day gap in DM/Q therapy between DB and open-label experienced a return of symptoms. Results here support prolonged effectiveness of DM/Q as PBA treatment. Study Supported by: Avanir Pharmaceuticals, Inc. Disclosure: Dr. Rix Brooks has nothing to disclose. Dr. Pioro has nothing to disclose. Dr. Shin has received personal compensation for activities with Avanir Pharmaceuticals, Inc. as an employee. Dr. Law has received personal compensation for activities with Avanir Pharmaceuticals, Inc. as an employee. Dr. Formella has received personal compensation for activities with Avanir Pharmaceuticals, Inc. as an employee.