From the Guidelines
Dextromethorphan, in combination with quinidine, is effective in treating pseudobulbar affect (PBA), as evidenced by its approval by the FDA in the form of Nuedexta 1. The use of dextromethorphan alone is not recommended due to its rapid first-pass metabolism, which makes it difficult to achieve therapeutic levels in the brain without quinidine. Key points to consider in the treatment of PBA include:
- The importance of quinidine in inhibiting the metabolism of dextromethorphan, allowing it to reach therapeutic levels 1.
- The potential for significant side effects with high doses of dextromethorphan, including dizziness, sedation, and abuse concerns.
- Alternative approaches, such as SSRIs or tricyclic antidepressants, may be considered if Nuedexta is unavailable or contraindicated, although these are used off-label. The American Heart Association/American Stroke Association guidelines suggest a therapeutic trial of dextromethorphan/quinidine for patients with emotional lability or pseudobulbar affect causing emotional distress 1. In clinical practice, it is essential to prioritize the use of FDA-approved medications, such as Nuedexta, for the treatment of PBA to ensure optimal management of symptoms and improvement in quality of life.
From the Research
Efficacy of Dextromethorphan in Treating Pseudobulbar Affect (PBA)
- Dextromethorphan/quinidine has been shown to be effective in reducing the rate of PBA episodes and improving PBA severity in adults with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) 2.
- A 12-week, double-blind, placebo-controlled trial in adults with ALS or MS demonstrated significant improvements in PBA severity with dextromethorphan/quinidine treatment 2.
- An open-label study (PRISM II) found that dextromethorphan/quinidine significantly reduced PBA symptoms in patients with dementia, with a mean reduction of 7.2 points in Center for Neurologic Study-Lability Scale (CNS-LS) score at Day 90/Endpoint 3.
- Another study found that dextromethorphan/quinidine was effective in reducing PBA episodes in patients with traumatic brain injury (TBI), with a significant mean reduction in CNS-LS score from baseline to day 90 4.
Safety and Tolerability
- Dextromethorphan/quinidine was generally well tolerated in clinical trials, with no particular safety or tolerability concerns 2.
- Common adverse events associated with dextromethorphan/quinidine treatment included headache, urinary tract infection, and diarrhea 3, 4.
- A case report found that dextromethorphan/quinidine was effective in treating PBA in a patient with a history of TBI, partial brain resection, and brainstem stroke, with no deleterious side effects 5.
Clinical Implications
- Dextromethorphan/quinidine is a useful option in the treatment of adults with PBA, particularly those with ALS, MS, dementia, or TBI 2, 3, 4.
- The combination of dextromethorphan and quinidine enables high plasma dextromethorphan concentrations to be reached without using a larger dose of the drug, making it a effective treatment for PBA 2, 6.