What is the recommended treatment and dosage for pseudobulbar affect (PBA) using Nudexta (dextromethorphan and quinidine)?

Recommended Treatment and Dosage for Pseudobulbar Affect (PBA) Using Nuedexta

The recommended treatment for pseudobulbar affect (PBA) is Nuedexta (dextromethorphan/quinidine) at a dosage of 20 mg dextromethorphan/10 mg quinidine taken twice daily. 1

Understanding Pseudobulbar Affect

Pseudobulbar affect (PBA) is a neuropsychiatric condition characterized by:

• Uncontrollable, inappropriate episodes of laughing and/or crying
• Emotional expressions that are either unrelated or disproportionate to the patient's actual feelings
• Occurs in patients with underlying neurological conditions such as:
  • Amyotrophic lateral sclerosis (ALS)
  • Multiple sclerosis (MS)
  • Stroke
  • Traumatic brain injury
  • Alzheimer's disease
  • Parkinson's disease

Treatment Protocol with Nuedexta

Dosage and Administration

• Starting dose: 20 mg dextromethorphan/10 mg quinidine twice daily
• No titration period is required
• Administer at regular intervals approximately 12 hours apart
• Can be taken with or without food

Mechanism of Action

Nuedexta works through a dual mechanism:

1. Dextromethorphan: Acts as an NMDA receptor antagonist and sigma-1 receptor agonist, affecting emotional regulation pathways
2. Quinidine: Serves to inhibit the metabolism of dextromethorphan by CYP2D6 enzymes, allowing therapeutic plasma levels of dextromethorphan to be achieved 2

Clinical Evidence Supporting Nuedexta for PBA

The efficacy of Nuedexta has been demonstrated in several key studies:

1. STAR Trial: A 12-week, double-blind, placebo-controlled study in patients with PBA due to ALS or MS showed:

   • Significant reduction in PBA episode rates
   • Improved PBA severity scores
   • Continued improvement during a 12-week extension phase 3

2. PRISM II Trial: A 12-week study demonstrated effectiveness in PBA secondary to dementia 2

3. Case Reports: Complete resolution of symptoms has been documented in patients with complex neurological histories, including those with traumatic brain injury and brainstem stroke 4

Monitoring and Safety Considerations

Precautions

• QT Prolongation: Nuedexta can cause dose-dependent QTc interval prolongation

  • Monitor ECG in patients with cardiac risk factors
  • Avoid in patients with complete heart block or significant QT prolongation
  • Use caution with other medications that may prolong QT interval

• Drug Interactions:

  • Avoid concomitant use with MAO inhibitors
  • Use caution with drugs metabolized by CYP2D6
  • Potential interactions with other quinidine-containing products

Common Side Effects

• Dizziness
• Nausea
• Headache
• Fatigue
• Diarrhea

Alternative Treatments for PBA

If Nuedexta is contraindicated or not tolerated, alternative options include:

1. Antidepressants:

   • Tricyclic antidepressants (TCAs)
   • Selective serotonin reuptake inhibitors (SSRIs)

   However, these medications have not been studied in controlled trials specifically for PBA, and their efficacy remains uncertain 4

Follow-up and Treatment Evaluation

• Assess response to treatment after 4-6 weeks
• Use standardized scales such as the Center for Neurologic Study-Lability Scale (CNS-LS) to quantify improvement
• Continue treatment if beneficial with periodic reassessment
• Consider discontinuation if no improvement after 12 weeks of therapy

Conclusion

Nuedexta represents the first FDA-approved treatment specifically for PBA. The recommended dosage of 20 mg dextromethorphan/10 mg quinidine twice daily provides effective symptom control with an acceptable safety profile. While traditional antidepressants have been used historically, the evidence supporting Nuedexta makes it the preferred first-line treatment for patients with PBA.