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

Abstract

BackgroundPhase 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).MethodsParticipants 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).ResultsThe 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.ConclusionsDM/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 registrationClinicaltrials.gov, NCT01799941, registered on 25 February 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0609-0) contains supplementary material, which is available to authorized users.

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

“…Patients treated with DM/Q 20/10 mg experienced improvements across multiple assessments, including significant reductions in CNS‐LS scores and PBA episodes, improvements in CGI‐C and PGI‐C, SIS, QOL‐VAS, MMSE, and PHQ‐9. These results were consistent with those for other PRISM II patient cohorts with PBA following dementia or TBI . Further, an a priori analysis comparing results from this open‐label trial with results from placebo‐controlled phase 3 studies enrolling patients with PBA caused by ALS or MS showed a consistent effect based on confidence intervals for change from baseline mean CNS‐LS .…”

“…The Pseudobulbar Affect Registry Investigating Symptom Management II (PRISM II) was designed to evaluate DM/Q effectiveness and safety for PBA treatment in patients with stroke, traumatic brain injury (TBI), or dementia—3 neurologic conditions that commonly cause PBA. Results from the overall study population (N = 367) as well as the cohort of PBA patients with dementia (n = 134) have been reported previously . Safety, tolerability, and efficacy results for the patients with PBA following stroke are reported here.…”

Neuroprotective effect of berberine agonist against impairment of learning and memory skills in severe traumatic brain injury via Sirt1/p38 MAPK expression

“…The fatality and disability rates of TBI are the highest among traumas of human organs (1). The incidence of TBI in USA is ~2%, and 500,000 new TBI cases are recorded annually, including 10% severe TBI, which leads to ~20,000 mortality and 30,000 disability cases, resulting in significant direct and indirect economic losses (2). With the rapid development of the global economy and modern transportation, TBI has become an important human health issue (1).…”

Pseudobulbar Affect Correlates With Mood Symptoms in Parkinsonian Disorders but Not Amyotrophic Lateral Sclerosis

“…Although PBA is considered an affective disorder independent of mood, both antidepressants (such as serotonin reuptake inhibitors and tricyclic antidepressants) and dextromethorphan/quinidine (DM/Q) are known to be effective in the treatment of PBA symptoms. [18][19][20] The mood effects of DM/Q are not established, and our findings suggest the possibility that patients with parkinsonism could preferentially benefit from treatment with antidepressants for dual management of both PBA and mood symptoms with a single agent.…”