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.