Dextromethorphan Plus Ultra Low-Dose Quinidine Reduces Pseudobulbar Affect
Version of Record online: 13 SEP 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 68, Issue 5, pages 693–702, November 2010
How to Cite
Pioro, E. P., Brooks, B. R., Cummings, J., Schiffer, R., Thisted, R. A., Wynn, D., Hepner, A. and Kaye, R. (2010), Dextromethorphan Plus Ultra Low-Dose Quinidine Reduces Pseudobulbar Affect. Ann Neurol., 68: 693–702. doi: 10.1002/ana.22093
- Issue online: 28 OCT 2010
- Version of Record online: 13 SEP 2010
- Manuscript Accepted: 20 MAY 2010
- Manuscript Revised: 30 APR 2010
- Manuscript Received: 24 FEB 2010
To evaluate dextromethorphan combined with ultra low-dose quinidine (DMq) for treating pseudobulbar affect (PBA) in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS).
In a 12-week randomized, double-blind trial, ALS and MS patients with clinically significant PBA (a baseline score ≥13 on the Center for Neurologic Studies–Lability Scale [CNS-LS]) were maintained, twice daily, on placebo, DMq at 30/10mg (DMq-30), or DMq at 20/10mg (DMq-20).
In 326 randomized patients (of whom 283, or 86.8%, completed the study), the PBA-episode daily rate was 46.9% (p < 0.0001) lower for DMq-30 than for placebo and 49.0% (p < 0.0001) lower for DMq-20 than for placebo by longitudinal negative binomial regression, the prespecified primary analysis. Mean CNS-LS scores decreased by 8.2 points for DMq-30 and 8.2 for DMq-20, vs 5.7 for placebo (p= 0.0002 and p= 0.0113, respectively). Other endpoints showing statistically significant DMq benefit included, for both dosage levels, the likelihood of PBA remission during the final 14 days and, for the higher dosage, improvement on measures of social functioning and mental health. Both dosages were safe and well tolerated.
DMq markedly reduced PBA frequency and severity, decreasing the condition's detrimental impact on a patient's life, with satisfactory safety and high tolerability. The findings expand the clinical evidence that DMq may be an important treatment for patients suffering from the socially debilitating symptoms of PBA. Ann Neurol 2010