Introduction: Pseudobulbar affect (PBA) is characterized by sudden, frequent, uncontrollable laughing/crying episodes that are out of proportion or disconnected from mood or social context. PRISM-II evaluated dextromethorphan/quinidine (DM/Q) effectiveness for PBA secondary to stroke (reported here), dementia, or traumatic brain injury.
Hypothesis: DM/Q is effective and well tolerated for PBA secondary to neurologic disease such as stroke.
Methods: Open-label, 12-week, US multicenter trial of DM/Q 20/10 mg twice/day (starting once/day in week 1). Eligible patients had PBA with Center for Neurologic Study-Lability Scale (CNS-LS) ≥13 (range 7-35), were ≥3 months post-stroke (ischemic or hemorrhagic) and neurologically stable. Primary endpoint: CNS-LS change at Day 90/early withdrawal; secondary endpoints: PBA episode count, CGI-C, PGI-C, PHQ-9, QOL-VAS, patient satisfaction, MMSE, Stroke Impact Scale, and adverse events.
Results: 113 enrolled; 91 (80.5%) completed. CNS-LS improved by mean [95% CI] -7.6 [-9.0, -6.2] points at Day 90/endpoint from baseline mean (SD) of 20.8 (4.7), P<.001 vs baseline. PBA baseline mean (SD) weekly episode count of 19.6 (29.6) was reduced by 75.5% at Day 90/endpoint (P<.001 vs baseline). Patients or clinicians reported “much” or “very much” improvement with respect to PBA in 67.7% (PGI-C) and 75.0% (CGI-C) of patients. Improvements were also seen for PHQ-9, QOL-VAS and MMSE. All Stroke Impact Scale domain scores improved vs baseline (P=.02 to P<.001); Adverse events were reported by 40 (35.4%), assessed as treatment-related in 16 (14.2%), and led to discontinuation in 6 (5.3%).
Conclusion: Consistent with the approved indication, DM/Q improved PBA symptoms, reduced frequency of PBA episodes and was well tolerated in patients with PBA secondary to stroke. CNS-LS change from baseline was similar to that seen with DM/Q in a Phase 3 trial in ALS or MS (mean change [95% CI] -8.2 [-9.4, -7.0]) and greater than improvement with placebo in that trial (mean change -5.7[-6.8,-4.7]). DM/Q was associated with global clinical improvements (PGI-C, CGI-C), along with improvements in cognition, depressive symptoms, stroke-related function and quality of life. Supported by: Avanir Pharmaceuticals, Inc.