From the Research
The first-line treatment for pseudobulbar affect (PBA) is dextromethorphan/quinidine (Nuedexta), which is specifically FDA-approved for this condition. The standard dosage is one capsule containing 20 mg dextromethorphan and 10 mg quinidine taken once daily for the first week, then increased to twice daily thereafter. This combination works by modulating neurotransmitters in the brain, with dextromethorphan acting on sigma-1 receptors and NMDA receptors while quinidine prevents the rapid metabolism of dextromethorphan 1.
Key Considerations
- Before starting treatment, patients should undergo cardiac evaluation as quinidine can prolong the QT interval 2.
- Common side effects include dizziness, diarrhea, and nausea.
- For patients who cannot tolerate or have contraindications to Nuedexta, alternative options include selective serotonin reuptake inhibitors (SSRIs) like citalopram or fluoxetine, or tricyclic antidepressants like amitriptyline, though these are used off-label 3.
- Treatment should continue as long as symptoms persist, with periodic reassessment of the need for ongoing therapy.
Mechanism and Efficacy
The efficacy of dextromethorphan/quinidine in treating PBA has been demonstrated in several studies, including a 12-week, double-blind, placebo-controlled trial in adults with ALS or MS, where it reduced the rate of PBA episodes and improved PBA severity 1. The combination of dextromethorphan and quinidine has been shown to be safe and well-tolerated, with no particular safety or tolerability concerns 2.
Recent Findings
A more recent study published in 2016 suggests that dextromethorphan-quinidine may also be effective in treating other disorders of emotional expression, given its mechanism of action on sigma, glutamate, and serotonergic pathways 4. However, the primary recommendation for PBA treatment remains focused on dextromethorphan/quinidine due to its specific FDA approval and demonstrated efficacy for this condition.