Abstract: | BackgroundDextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI).ObjectiveTo report results from the TBI cohort of PRISM II, including a TBI-specific functional scale.DesignOpen-label trial evaluating twice-daily DM/Q over 90 days.Study ParticipantsAdults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed.MethodsPRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90.Setting150 U.S. centers.Main Outcome MeasurementsPrimary endpoint was change in Center for Neurologic Study–Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life–Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE).ResultsDM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, –5.6 5.2]; day 90, –8.5 5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had “much improved” or “very much improved” on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (–3.7 3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (–3.2 5.3], P<.001) and 90 (–5.2 6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%).ConclusionsDM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials.Level of EvidenceII |