Additional evidence for a therapeutic effect of dextromethorphan/quinidine on bulbar motor function in patients with amyotrophic lateral sclerosis: A quantitative speech analysis

AIMS A recent double-blind placebo-controlled crossover 70-day trial demonstrated that a fixed combination of dextromethorphan and quinidine (DM/Q) improves speech and swallowing function in most patients with amyotrophic lateral sclerosis. In this study, a subset of participants, many of whom did not substantially improve while on DM/Q, were re-evaluated using computer-based speech analyses and expert clinician ratings of the overall severity of speech impairment. METHODS Speech samples were recorded from the subset of 10 patients at four visits made at approximately 30-day intervals. The recordings were analysed by automated computer-based analysis of speech pausing patterns. Severity of speech impairment was rated by three experienced speech-language pathologists using direct magnitude estimation. Scores on patient-reported and clinician-administered scales of bulbar motor involvement were obtained at each visit. RESULTS The effects of DM/Q were detected on several of the objective speech measures, including total pause duration (s) (Cohen's d = 0.73, 95% confidence interval (CI) -1.70, 0.24), pause time (%) (d = 0.77, 95% CI -1.75, 0.21), and mean speech event duration (s) (d = 0.52, 95% CI -0.44, 1.47), but not on clinician ratings of speech or the speech components of the self-report or clinician-administered scales. CONCLUSIONS These findings suggest that even patients with modest improvement while on DM/Q may experience quantifiable improvements in speech when assessed using sensitive and objective measures. This study provides additional evidence of the positive impact of DM/Q on one or more of the neural systems that control bulbar motor function and production of speech.