Background: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar\naffect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II\nstudy provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI).\nMethods: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary\noutcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and\nseverity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously\nconducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in\nPBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by\nthe patient or caregiver (PGI-C).\nResults: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation\n[SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, âË?â??7.7 [6.1]; P\n< .001, 95 % CI: âË?â??8.4, âË?â??7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier\nphase-3, placebo-controlled trial (mean [95 % CI] change from baseline, âË?â??8.2 [âË?â??9.4, âË?â??7.0]) and numerically exceeds the\nimprovement seen with placebo in that study (âË?â??5.7 [âË?â??6.8, âË?â??4.7]). Reduction in PBA episode count was 72.3 % at Day\n90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants,\nrespectively, were ââ?¬Å?muchââ?¬Â or ââ?¬Âvery muchââ?¬Â improved with respect to PBA. The most frequently occurring adverse events\n(AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to\ndiscontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related.\nConclusions: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or\nTBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and\nthe adverse event profile was consistent with the known safety profile of DM/Q.
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