Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect.
OBJECTIVE
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).


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Pioro
Erik P
EP
Section of ALS and Related Disorders, Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH 44195, USA. PIOROE@ccf.org
Brooks
Benjamin Rix
BR
Cummings
Jeffrey
J
Schiffer
Randolph
R
Thisted
Ronald A
RA
Wynn
Daniel
D
Hepner
Adrian
A
Kaye
Randall
R
D000293:Adolescent; D000328:Adult; D000342:Affective Symptoms / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications; D003915:Dextromethorphan / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications; D010100:Oxygen / Q000097:blood; D011802:Quinidine / Q000008:administration & dosage* / Q000009:adverse effects
D004338:Drug Combinations; D003915:Dextromethorphan; D011802:Quinidine; D010100:Oxygen