Dextromethorphan/quinidine for the treatment of bulbar impairment in amyotrophic lateral sclerosis

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Abstract
Objective: No efficacious treatments exist to improve or prolong bulbar functions of speech and swallowing in persons with amyotrophic lateral sclerosis (pALS). This study evaluated the short‐term impact of dextromethorphan/quinidine (DMQ) treatment on speech and swallowing function in pALS.Methods: This was a cohort trial conducted between August 2019 to August 2021 in pALS with a confirmed diagnosis of probable‐definite ALS (El‐Escorial Criteria‐revisited) and bulbar impairment (ALS Functional Rating Scale score ≤ 10 and speaking rate ≤ 140 words per minute) who were DMQ naïve. Efficacy of DMQ was assessed via pre‐post change in the ALS Functional Rating Scale‐Revised bulbar subscale and validated speech and swallowing outcomes. Paired t‐tests, Fisher's exact, and χ2 tests were conducted with alpha at 0.05.Results: Twenty‐eight pALS enrolled, and 24 participants completed the 28‐day trial of DMQ. A significant increase in ALSFRS‐R bulbar subscale score pre‐ (7.47 ± 1.98) to post‐ (8.39 ± 1.79) treatment was observed (mean difference: 0.92, 95% CI: 0.46–1.36, p < 0.001). Functional swallowing outcomes improved, with a reduction in unsafe (75% vs. 44%, p = 0.003) and inefficient swallowing (67% vs. 58%, p = 0.002); the relative speech event duration in a standard reading passage increased, indicating a greater duration of uninterrupted speech (mean difference: 0.33 s, 95% CI: 0.02–0.65, p = 0.035). No differences in diadochokinetic rate or speech intelligibility were observed (p > 0.05).Interpretation: Results of this study provide preliminary evidence that DMQ pharmacologic intervention may have the potential to improve or maintain bulbar function in pALS.

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