Management of Huntington's Disease Chorea
Tetrabenazine, deutetrabenazine (Austedo), and valbenazine (Ingrezza) are the most effective medications for treating chorea in Huntington's disease, with tetrabenazine being FDA-approved specifically for this purpose. 1
First-Line Pharmacological Management
Tetrabenazine (FDA-approved)
- Start at 12.5 mg once daily in the morning
- Titrate slowly by 12.5 mg weekly to identify tolerated dose that reduces chorea
- For doses 37.5-50 mg/day, use three times daily dosing
- Maximum recommended single dose: 25 mg
- For doses >50 mg/day, CYP2D6 genotyping is required:
- Extensive/intermediate metabolizers: can titrate up to 100 mg/day (maximum single dose: 37.5 mg)
- Poor metabolizers: should not exceed 50 mg/day 2
Alternative VMAT2 Inhibitors
- Deutetrabenazine (Austedo): Better tolerability profile than tetrabenazine 1
- Valbenazine (Ingrezza): May have improved side effect profile 1
Monitoring and Safety Considerations
Critical Safety Monitoring
- Depression and suicidality: Close observation required as tetrabenazine can increase risk of depression and suicidal thoughts 2
- Screen for depression before and during treatment
- Contraindicated in actively suicidal patients or those with untreated/inadequately treated depression 2
- Monitor for:
- Akathisia, restlessness, parkinsonism (reduce dose if these occur)
- Swallowing function (aspiration pneumonia is a common fatal complication)
- Sleep patterns
- Cognitive function 1
Drug Interactions
- Strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) significantly increase exposure to tetrabenazine metabolites 2
- Consider antipsychotics for patients with prominent psychiatric symptoms alongside chorea 1
Alternative Approaches for Chorea
Antipsychotics
- Haloperidol, sulpiride, and quetiapine provide dual benefit for both chorea and psychiatric symptoms 1
- Particularly useful when psychiatric symptoms are prominent
Emerging Therapies
Recent advances in gene and cell therapy strategies show promise but remain investigational:
- Antisense Oligonucleotide (ASO) therapy targets reduction of mutant huntingtin protein levels 1
- CRISPR-based approaches targeting CAG repeat expansion at the DNA level 3
- RNA-targeting CRISPR systems (CRISPR-Cas13d) show potential for allele-selective suppression of mutant HTT 3
- Small molecule splice modulators are being explored as alternatives that can cross the blood-brain barrier 3
Comprehensive Management Approach
- Regular assessment of motor symptoms, psychiatric symptoms, and cognitive function
- Address psychiatric symptoms promptly with appropriate medications
- Monitor for common complications, particularly swallowing difficulties
- Employ a multidisciplinary approach including physical, occupational, and speech therapy as needed
While current treatments focus on symptom management, ongoing research into disease-modifying therapies offers hope for future interventions that may alter the course of the disease.