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).

METHODS

Open-label trial evaluating twice-daily DM/Q over 90 days.

METHODS

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.

METHODS

150 U.S. centers.

METHODS

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.