Dextromethorphan/Quinidine: A Review of Its Use in Adults with Pseudobulbar Affect

Abstract

Fixed-dose dextromethorphan/quinidine capsules (Nuedexta(®)) utilize quinidine to inhibit the metabolism of dextromethorphan, enabling high plasma dextromethorphan concentrations to be reached without using a larger dose of the drug. The drug combination is the first treatment to be approved for pseudobulbar affect (PBA), a condition of contextually inappropriate/exaggerated emotional expression that often occurs in adults with neurological damage conditions, such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, traumatic brain injury, Alzheimer's disease or Parkinson's disease. Dextromethorphan/quinidine at the recommended dosages of 20/10 or 30/10 mg twice daily reduced the rate of PBA episodes and improved PBA severity in a 12-week, double-blind, placebo-controlled trial in adults with ALS or MS (STAR), with further improvements in the severity of the condition observed in a 12-week open-label extension phase. Dextromethorphan/quinidine 20/10 mg twice daily also improved PBA secondary to dementia in a cohort of a 12-week noncomparative trial (PRISM II). The drug combination was generally well tolerated in these studies, with no particular safety or tolerability concerns. Although longer-term efficacy and tolerability data for dextromethorphan/quinidine 20/10 or 30/10 mg twice daily would be beneficial, current evidence indicates that it is a useful option in the treatment of adults with PBA.

Enhanced Bulbar Function in Amyotrophic Lateral Sclerosis: The Nuedexta Treatment Trial

“…As DMQ is an approved drug with an excellent safety profile [22], baseline laboratory studies were limited to a complete blood count, standard chemistry panel, and an electrocardiogram. The occurrence of adverse events was documented at each study visit, as well as at a final follow-up telephone call.…”

Geriatrics update 2015: Vaccination, frailty, chronic disease guidelines, and cognition

“…Using a 20/10-mg dose combination, a small 12-week noncomparative trial demonstrated measurable improvement in pseudobulbar symptoms after 30 days (as measured by the Center for Neurologic Study-Lability Scale). 21 Though individuals enrolled in this trial appeared to tolerate this dose, additional trials still need to be conducted to more clearly determine its long-term safety and efficacy. It is not approved for dementia with agitation, but a phase 2 trial suggests a benefit compared with placebo in reducing agitation and caregiver burden.…”

Nondopaminergic Treatments for Parkinson’s Disease: Current and Future Prospects

“…Dextromethorphan is another NMDA receptor antagonist that has been combined with quinidine, a CYP2D6 inhibitor responsible for reducing and stabilizing the metabolism of dextromethorphan into a single drug preparation. This combination of dextromethorphan combined with quinidine (AVP923) is clinically available in the USA for treatment of pseudobulbar affect [77]. Due to the clinical availability of this agent, and earlier studies showing efficacy, a small Phase IIa study in PD to treat LID is ongoing (Table 1) [18,78].…”