What are the management options for Huntington's disease?

Management Options for Huntington's Disease

The management of Huntington's disease requires a combination of pharmacological and non-pharmacological interventions targeting symptom relief, as there is currently no curative treatment available. 1

Pharmacological Management of Chorea

First-line Medications

• Tetrabenazine: FDA-approved specifically for HD chorea

  • Starting dose: 12.5 mg/day given once in the morning
  • Titrate slowly at weekly intervals by 12.5 mg daily
  • Typical effective dose: 25-75 mg/day
  • Maximum recommended daily dose: 100 mg (for extensive metabolizers)
  • Maximum single dose: 37.5 mg 2
  • Clinical trials showed significant reduction in Total Chorea Scores compared to placebo 2

• Deutetrabenazine (Austedo): Better tolerability profile than tetrabenazine 3

• Valbenazine (Ingrezza): May have improved side effect profile 3

For Patients with Psychiatric Symptoms

• Antipsychotics with antichorea effects provide dual benefit:
  • Haloperidol
  • Sulpiride
  • Quetiapine 3

Management of Psychiatric Symptoms

Psychiatric symptoms occur in 33-76% of patients and can appear up to 20 years before motor symptoms 4:

• Depression and Suicidality:

  • Require close monitoring and aggressive treatment
  • Antidepressants should be initiated promptly when symptoms appear
  • Regular screening for depression and suicidality is essential 2

• Irritability and Aggression:

  • Mood stabilizers or atypical antipsychotics
  • Environmental modifications to reduce triggers

• Anxiety:

  • SSRIs or benzodiazepines (with caution due to potential for cognitive side effects)

• Apathy:

  • Often difficult to treat
  • Consider stimulants in selected cases

Cognitive Management

• Cognitive symptoms progressively worsen and require:
  • Cognitive exercises and environmental adaptations
  • Simplification of daily tasks
  • Caution with medications that may worsen cognition

Emerging Therapies

• Antisense Oligonucleotide (ASO) therapy:

  • Targets reduction of mutant huntingtin protein levels
  • Tominersen showed initial promise in reducing mHTT in CSF but has faced development challenges 1

• Gene therapy approaches:

  • Target CAG repeat expansion at DNA level
  • Aim to correct or delete the mutated HTT gene 1

• Experimental compounds:

  • Curcumin: May ameliorate immune and metabolic dysregulation 1
  • Ganglioside GM1: Shows promise in restoring motor function in animal models 1

Monitoring and Follow-up

• Regular assessment of:
  • Motor symptoms (particularly chorea)
  • Psychiatric symptoms (depression, anxiety, psychosis)
  • Cognitive function
  • Swallowing function (to prevent aspiration pneumonia, a common cause of mortality) 1
  • Sleep patterns
  • Medication side effects

Multidisciplinary Care

• Physical therapy: Maintain mobility and prevent falls
• Occupational therapy: Adaptive strategies for activities of daily living
• Speech therapy: Address communication and swallowing difficulties
• Nutritional support: Manage weight loss and swallowing difficulties
• Social work: Assist with practical difficulties faced by patients and caregivers 5
• Genetic counseling: Essential for family members 6

Common Pitfalls and Caveats

1. Medication side effects: Tetrabenazine and antipsychotics can worsen depression, parkinsonism, and sedation; regular reassessment is crucial 2

2. Suicidality risk: Tetrabenazine carries a black box warning for depression and suicidality; close monitoring is required 2

3. CYP2D6 metabolizer status: Should be determined before prescribing tetrabenazine doses >50 mg/day 2

4. Cognitive impact: Some medications for chorea may negatively impact cognitive function; balance symptom control with cognitive preservation 2

5. Disease progression: Treatment plans need regular adjustment as the disease progresses and symptoms evolve 6

6. Aspiration pneumonia: A common fatal complication requiring vigilant monitoring of swallowing function 1