PHILADELPHIA—Patients with pseudobulbar affect who take dextromethorphan and quinidine are significantly more likely to enter remission, compared with patients receiving placebo, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. Remission may occur within the first three weeks of treatment.
Approximately 19% of participants taking 20 mg of dextromethorphan and 10 mg of quinidine reported no further episodes of pseudobulbar affect after the first week of a 12-week trial, said Benjamin Rix Brooks, MD, a neurologist at Carolinas Neuromuscular Disease/ALS-MDA Center in Charlotte, North Carolina. The percentage of individuals treated with dextromethorphan and quinidine who entered remission increased gradually after the first week and was 51% by the end of the study, he added.
Pseudobulbar affect is characterized by frequent, uncontrollable episodes of laughing or crying that are inconsistent with the patient’s emotional state. A combination of dextromethorphan and quinidine is the only approved medication for pseudobulbar affect treatment in the United States and the European Union.
Post Hoc Analysis of a Pivotal Trial
The results that Dr. Brooks presented were for a secondary outcome of the pivotal trial of dextromethorphan and quinidine that he and his colleagues conducted. The study’s primary outcome was the change from baseline in laughing and crying episodes per day, as recorded in patient diaries. These results were published in Annals of Neurology in 2010.
The investigators randomized 197 patients with amyotrophic lateral sclerosis and 129 patients with multiple sclerosis to 30 mg of dextromethorphan and 10 mg of quinidine twice daily, 20 mg of dextromethorphan and 10 mg of quinidine twice daily, or placebo.
Participants were between the ages of 18 and 80 and had clinically significant pseudobulbar affect. Patient characteristics were similar among the three study arms. Dosing occurred once daily during the trial’s first week and twice daily thereafter.
Sustained remission was defined prospectively as cessation of pseudobulbar affect episodes during the final 14 days of study participation. The investigators gauged the percentage of patients entering remission at each study week.
Dr. Brooks and colleagues conducted a post hoc analysis to assess the time to sustained remission for patients who received the FDA-approved dose of 20 mg of dextromethorphan and 10 mg of quinidine, versus placebo.
Differences in Remission Rates Emerged Early
Approximately half of the patients randomized to 20 mg of dextromethorphan and 10 mg of quinidine reported remission. During week 1, the number of patients entering remission was three times higher among patients receiving 20 mg of dextromethorphan and 10 mg of quinidine than among controls. Differences in the percentage of patients entering remission remained significant until the end of the study. “It was an early change,” said Dr. Brooks. “We saw it in the first, second, and third weeks, compared with the placebo group.”
“Remission is a sustainable outcome measure” for treatment with dextromethorphan and quinidine, continued Dr. Brooks. “The issue of whether there could be breakthrough [symptoms] should be looked at in phase III studies.”
—Erik Greb