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

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.