Dextromethorphan/Quinidine for Managing Respiratory Impairment in ALS

In patients with amyotrophic lateral sclerosis (ALS), treatment with dextromethorphan/quinidine (DM/Q) was not shown to prevent failure of noninvasive respiratory management and had no effect on long-term deterioration of bulbar function, according to the results of a prospective, case-cohort study published in Respiratory Medicine.

Investigators sought to evaluate whether treatment with DM/Q could offer long-term improvement in bulbar impairment in individuals with ALS, thus prolonging the use of noninvasive respiratory muscle aids and increasing patient survival. They also assessed the long-term efficacy of DM/Q therapy on bulbar function and pseudobulbar affect in patients with ALS.

The current study was conducted between January 2017 and January 2019 in the respiratory care unit of a tertiary care hospital in Spain. The study included patients who had been diagnosed with ALS per revised El Escorial criteria. Study inclusion criteria were bulbar dysfunction (ie, a score of <39 on the Norris scale bulbar subscore [NBS], as well as a score of >13 on the Center for Neurologic Study Lability Scale [CNS-LS]). Neurologic functional assessment was conducted using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

The use of noninvasive respiratory muscle assistance failed in 28.5% of patients receiving dextromethorphan/quinidine vs 20.0% of those in the control group. Credit: Science Source Images

A total of 21 consecutive patients with ALS being treated with DM/Q and 20 historical cross-matched control patients with ALS were enrolled in the study. Treated patients received DM/Q 20/10 mg administered orally twice daily. Of the 21 DM/Q-treated patients with ALS, 10 were also receiving noninvasive ventilation (NIV) plus mechanically assisted cough (MIE) and 4 were using MIE only. In the control group, 5 individuals were using NIV plus MIE, 2 were using NIV only, and 1 was using MIE only.

Study results demonstrated that the use of noninvasive respiratory muscle assistance failed in 28.5% (6 of 21) of patients in the DM/Q group vs 20.0% (4 of 20) of those in the control group, a difference that was not statistically significant (P =.645). The time from onset of the study to failure of the respiratory muscle aids was 5.50±1.31 months in the DM/Q group compared with 5.50±1.15 months, a difference that also was not statistically significant (P =.663).

Regarding the effect of treatment on failure of noninvasive respiratory muscle aids, the unadjusted odds ratio (OR) was 1.47 (95% CI, 0.32-6.26; P =.646) and the adjusted OR was 2.12 (95% CI, 0.23-33.79; P =.592). Further, in the DM/Q arm, 6 patients required a tracheostomy during the study because of failure of the noninvasive respiratory management compared with 5 individuals in the control arm. No significant differences were observed in changes in NBS or ALSFRS-R scores.

Improvement in pseudobulbar affect, as measured with the CNS-LS, was observed in patients with ALS treated with DM/Q (P =.033), with differences between baseline values and those in the remaining months reported. No significant differences were reported, however, between measures obtained at 3, 6, 9,  and 12 months. Pseudobulbar affect scores were not able to be measured among those in the control group.

The researchers concluded that the results of the current study do show that DM/Q treatment improves pseudobulbar affect over 1 year of follow-up in patients with ALS. Future  studies are warranted to assess the utility of long-term DM/Q therapy for improvement of bulbar dysfunction among individuals with ALS.

Reference
Sancho J, Ferrer S, Burés E, et al. Effect of one-year dextromethorphan/quinidine treatment on management of respiratory impairment in amyotrophic lateral sclerosis. Respir Med. Published online July 7, 2021. doi:10.1016/j.rmed.2021.106536