Dextromethorphan/Quinidine Improved Symptoms of Pseudobulbar Affect Irrespective of Concomitant Antidepressant Use (P6.210)

Objective: To evaluate outcomes from a DM/Q effectiveness trial for PBA stratified by antidepressant use at baseline in an exploratory analysis. Background: Pseudobulbar affect (PBA) can occur secondary to neurological diseases or brain injury and is characterized by frequent, uncontrollable laughing/crying episodes that are exaggerated or incongruent to mood or social context. PBA may be mistaken for, or occur comorbidly with, depression, and many patients receive antidepressant therapy. Dextromethorphan hydrobromide/quinidine sulfate (DM/Q) is currently the only approved PBA treatment (US). Design/Methods: In the open-label PRISM II study, persons with PBA secondary to dementia, stroke, or traumatic brain injury (TBI) were treated with DM/Q 20/10 mg BID for 90 days. Patients taking stable dosages of antidepressants were eligible. Outcome measures included the Center for Neurologic Study Lability Scale (CNS-LS) score (primary), PBA episode counts, QoL-Visual Analog Scale, PHQ-9, and MMSE. Mean change from baseline to Day 90 for antidepressant users vs non-users were analyzed for all patients and by neurologic disease cohort using ANCOVA with baseline score as a covariate. Results: A total of 367 patients enrolled, including 120, 113, and 134, with TBI, stroke, and dementia, respectively, 48.5% [42.5%, 45.1%, and 56.7%, respectively] were using antidepressants. Significant improvements were observed for all outcome measures, regardless of antidepressant use. CNS-LS change was −8.2 for antidepressant users vs −7.2 for non-users ( P =.08); results were similar by neurologic disease cohort. Improvement in other outcomes did not differ by antidepressant use, except mean change in MMSE in the stroke cohort [0.5, antidepressant users vs 1.7, non-users, P =.02]. AEs were reported for 37.6% of antidepressant users and 34.4% of non-users. Serious AEs were reported for 5.6% vs 6.9% and AEs leading to discontinuation for 7.9% vs 11.6% of antidepressant users vs non-users. Conclusions: In this analysis, DM/Q was associated with PBA symptom improvement regardless of concomitant antidepressant use at baseline. Study Supported by: Avanir Pharmaceuticals, Inc. Disclosure: Dr. Formella has received personal compensation for activities with Avanir Pharmaceuticals, Inc. as an employee. Dr. Alexander has nothing to disclose. Dr. Cutler has received personal compensation for activities with Acadia, Alkermes, Allergan, Arbor Pharmaceuticals, Avanir, Intra-Cellular Therapies, Ironshore, and Lundbeck. Dr. Cutler has received research support from Acadia, Akili, Interactive, Alkermes, Allergan, Avanir, Axsome, Intra-Cellular Therapies, Ironshore, Lundbeck, Medgenics, Neurocrine, Otsuka, Shire, Sunovion, Supernus, and Takeda. Dr. D9Amico has received personal compensation for activities with Avanir Pharmaceuticals, Inc., Sanofi Genzyme, Merck, AstraZeneca, Bristol-Myers, Novartis, and Takeda Pharmaceuticals. Dr. Hammond has received personal compensation for activities with Avanir Pharmaceuticals as an advisor. Dr. Sauve has received personal compensation for activities with Neuroscience Education Institute, Avanir Pharmaceuticals, Inc., Sunovion, Avanir Pharmaceuticals, Inc., and Otsuka as an advisor and speaker. Dr. Zorowitz has received personal compensation for activities with Avanir Pharmaceuticals. Dr. Zorowitz has received personal compensation in an editorial capacity for Archives of Physical Medicine and Rehabilitation, Stroke, and Topics in Stroke Rehabilitation. Dr. Zrowitz has received research support from SPR Therapeutics, Sunovion/Sanbio. Dr. Siffert has received personal compensation for activities with Avanir Pharmaceuticals as an employee.