title: Review of Dextromethorphan 20 mg/Quinidine 10 mg (NUEDEXTA(®)) for Pseudobulbar Affect.
abstract: Pseudobulbar affect (PBA) is a dysfunction of emotional expression characterized by involuntary outbursts of crying or laughing disproportionate or unrelated to mood, occurring in patients with various underlying neurologic disorders. This review describes the clinical data supporting dextromethorphan (DM) hydrobromide combined with quinidine sulfate (Q) as treatment of PBA and briefly surveys the ongoing debates concerning the terminology for dysfunction of emotional expression, as well as the ongoing searches for its brain substrates. Until recently, pharmacologic intervention consisted chiefly of off-label antidepressants. In October 2010, however, DM/Q at 20/10 mg twice daily received approval from the United States Food and Drug Administration for PBA in any setting, and in June 2013, dosages of 20/10 and 30/10 mg twice daily (labeled as 15/9 and 23/9 mg, respectively, DM/Q base) received approval from the European Medicines Agency. DM is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, a sigma-1 receptor agonist, and a serotonin and norepinephrine reuptake inhibitor. To block DM hepatic metabolism, thereby increasing DM bioavailability, Quinidine, a cytochrome P450 2D6 inhibitor, is coadministered at a dosage well below those for treating cardiac arrhythmia. Three large-scale DM/Q trials have utilized PBA-episode counts and the Center for Neurologic Study-Lability Scale (CNS-LS), a validated PBA rating scale, to measure efficacy. In a 4-week study of patients with PBA in amyotrophic lateral sclerosis (ALS), DM/Q 30/30 mg was superior to its component drugs. A 12-week, double-blind, placebo-controlled study of DM/Q 30/30 mg showed similar efficacy in patients with PBA in multiple sclerosis (MS). A subsequent 12-week study of patients with PBA and ALS or MS showed superiority to placebo for the 20/10 and 30/10 mg doses. Efficacy was maintained during a 12-week, open-label extension (30/10 mg dose), with further improvement of mean CNS-LS scores. Across these studies, DM/Q was generally safe and well tolerated, with no evidence of clinically relevant cardiac or respiratory effects. DM/Q is being studied (currently unapproved) for conditions including agitation in autism and in dementia.
authors.affiliation: Section of ALS and Related Disorders, Department of Neurology, S90, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 USA.
authors.forename: Erik P
authors.initials: EP
authors.lastname: Pioro
keywords: Center for Neurologic Study-Lability Scale (CNS-LS); Dysregulation; Involuntary crying and/or laughing; Neurologic disease; Neurologic injury; Pseudobulbar affect