PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury.

BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013.

Dextromethorphan/Quinidine for Pseudobulbar Affect Following Stroke: Safety and Effectiveness in the PRISM II Trial.

BACKGROUND: Dextromethorphan (DM) / quinidine (Q) was approved for pseudobulbar affect (PBA) treatment based on efficacy and safety trials in patients with PBA caused by amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial evaluated DM/Q as PBA treatment in patients with stroke, dementia, or traumatic brain injury. OBJECTIVE: To report results from the stroke cohort of PRISM II, including the Stroke Impact Scale (SIS). DESIGN: Open-label trial evaluating twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 113) with a clinical diagnosis of PBA secondary to stroke; stable psychiatric medications were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults with PBA caused by dementia, stroke (reported here), or TBI. All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at days 30 and 90. SETTING: 150 U.S. centers. MAIN OUTCOME MEASUREMENTS: Primary efficacy measure was changed from baseline to day 90 in Center for Neurologic Study-Lability Scale (CNS-LS) scores. Secondary outcomes included PBA episodes (estimated over 7 days), Clinical and Patient/Caregiver Global Impression of Change (CGI-C and PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), SIS, Patient Health Questionnaire (PHQ-9), and Mini-Mental State Examination (MMSE). RESULTS: Compared with baseline, CNS-LS scores (SD) improved by -6.2 (6.1, P < .001) at day 30 and -7.6 (6.7, P < .001) at day 90. PBA episodes were reduced by 65% and 75% at day 30 and 90, respectively. Seventy-five percent of clinicians and 67% of patients/caregivers rated PBA as "much" or "very much improved." All SIS items significantly improved from baseline (P < .05, all). Adverse events included diarrhea (4.4%), headache (3.5%), constipation (2.7%), and dizziness (2.7%); 5.3% had adverse events leading to study discontinuation. CONCLUSIONS: DM/Q effectively treated PBA and was associated with global and functional improvement; adverse events were consistent with the known safety profile of DM/Q.

Effects of acupuncture treatment on poststroke motor recovery and physical function: a pilot study.

This pilot study obtained preliminary data on the effects of acupuncture treatment combined with a standard inpatient stroke rehabilitation program on poststroke motor recovery and physical function. Thirty-two patients with acute stroke were recruited and randomized to 1 of 2 treatment arms: standard rehabilitation (control group) or a combination of acupuncture and standard rehabilitation (acupuncture group). Baseline and discharge assessments were obtained on motor recovery as measured by the Fugl-Meyer (FM) Assessment and on physical function as measured by the Functional Independence Measure (FIM). Comparisons were made between the acupuncture and control group in total FM and FIM as well as for each subscale of the FM and FIM. No differences between treatment groups were found in the total FM or the total FIM. However, statistically significant benefit due to acupuncture was observed for the FM lower extremity motor function subscale (P = 0.01) and the tub/shower transfer mobility subscale of the FIM (P = 0.03). Marginally significant benefit due to acupuncture was noted for the toilet transfer mobility subscale of the FIM (P = 0.09). The effectiveness of acupuncture as an adjunct to standard poststroke rehabilitation programs may be demonstrated when more specific measures of stroke motor recovery and physical function are used.