Dextromethorphan and Quinidine for Treatment of Pseudobulbar Affect (PBA): Time Course of PBA Episode Remission (S31.007)

Objective: Evaluate time to remission of pseudobulbar affect (PBA) episodes in a Phase III, placebo-controlled trial of dextromethorphan and quinidine. Background: PBA is a neurological condition characterized by frequent, uncontrollable episodes of laughing and/or crying that are incongruent to the patient’s emotional state. PBA is caused by brain diseases/injuries that damage neural pathways coordinating emotional expression. The condition is socially disabling and distressing to patients and others. PBA episode remission, defined as no episodes for 蠅14 days prior to endpoint, was a secondary outcome in a 12-week, double-blind, multicenter trial of dextromethorphan and quinidine vs. placebo. This post-hoc analysis assessed time to entering remission for the FDA-approved dose of dextromethorphan 20 mg/quinidine 10 mg (DMQ-20) given twice daily vs. placebo. Design/Methods: Patients were adults with clinically significant PBA secondary to amyotrophic lateral sclerosis or multiple sclerosis. DMQ-20 and placebo were dosed once daily for week 1 and twice daily thereafter. The percentage of patients entering remission, defined as no further PBA episodes in study + minimum 14 days without episodes prior to endpoint was assessed at each study week. Results: The trial randomized 107 patients to DMQ-20 and 109 to placebo. By Week 1, 18.7% of patients on DMQ-20 and 5.5% on placebo (P=.003; chi square) had entered remission (no further PBA episodes during the study). For Week 2 (first week of twice daily dosing) these percentages were 24.3% and 7.3%, respectively (P<.001). The cumulative percentage of remitters increased steadily at subsequent weeks. By trial endpoint, 51.4% on DMQ-20 and 29.4% on placebo were episode-free (P=.001) Conclusions: Approximately half of patients receiving DMQ-20 experienced PBA episode remission during this 12-week pivotal trial. Significant differences vs. placebo in the percentage of patients entering remission emerged early (Week 1) and remained significant in subsequent trial weeks. Study Supported by: Avanir Pharmaceuticals, Inc. Disclosure: Dr. Formella has received personal compensation for activities with Avanir Pharmaceuticals Inc. as an employee. Dr. Brooks has received personal compensation for activities with Biogen Idec, Avanir Pharmaceuticals, Acorda Therapeutics, Cytokinetics, Synapse, and the National Institute of Neurological Disorders and Stroke. Dr. Brooks has received research support from Biogen Idec, Avanir Pharmaceuticals, Cytokinetics, Neuraltus Pharmaceuticals, GlaxoSmithKline, Inc., and the National Institute of Neurological Disorders and Stroke.