What is the management and treatment approach for a patient with Huntington disease?

Management and Treatment of Huntington Disease

The management of Huntington disease requires symptomatic pharmacological treatment for chorea and psychiatric symptoms, combined with structured non-pharmacological interventions, while emerging gene therapies remain investigational. 1

Pharmacological Management

First-Line Treatment for Chorea

• Deutetrabenazine (Austedo) and valbenazine (Ingrezza) are the preferred FDA-approved agents for chorea management in HD patients. 1
• Tetrabenazine is an alternative dopamine-depleting agent that reduces chorea by an average of 3.5 units on the Total Chorea Score compared to placebo, though it carries risk of potentially serious adverse effects including depression and suicidality. 2
• The FDA trial demonstrated that 50% of tetrabenazine-treated patients achieved 6-point or greater improvement in chorea scores versus only 7% on placebo. 2
• Start tetrabenazine at 12.5 mg daily and titrate weekly in 12.5 mg increments until chorea control is achieved, side effects occur, or maximum dose of 100 mg daily is reached. 2

Management of Psychiatric and Behavioral Symptoms

• Antipsychotics (haloperidol, sulpiride, quetiapine) effectively manage both chorea and psychiatric symptoms including psychosis and severe behavioral disturbances. 1, 3
• Apply the "start low, go slow" principle when prescribing any medication for HD patients to minimize adverse effects. 3
• Antidepressants should be used for mood symptoms, with careful monitoring given the increased suicide risk in this population. 4

Non-Pharmacological Interventions (Implement Before Medications)

Environmental and Behavioral Strategies

• Establish predictable daily routines with consistent timing for meals, activities, and sleep to reduce confusion and anxiety. 1, 3
• Create a safe environment by removing hazards, installing safety locks on doors, and reducing environmental stimuli that trigger agitation. 1, 3
• Use the "three R's" approach: repeat instructions, reassure the patient, and redirect attention when managing behavioral disturbances. 3
• Break complex tasks into simple steps with clear, simple instructions for each step. 3
• Implement visual cues, calendars, and labels to help with orientation. 3

Multidisciplinary Care Requirements

• HD management requires active involvement of physicians, physical therapists, occupational therapists, speech therapists, social workers, and nutritionists. 5
• Physical therapy, speech therapy, and occupational therapy improve functional abilities and general well-being. 6
• Palliative care focusing on quality of life (physical, psychosocial, and spiritual problems) may delay nursing home placement in advanced HD. 5

Emerging Therapies (Currently Investigational)

Gene-Targeted Approaches

• Antisense oligonucleotide (ASO) therapy, specifically Tominersen, has demonstrated significant reduction of mutant huntingtin protein (mHTT) in cerebrospinal fluid in clinical trials, though development bottlenecks persist. 4, 1
• RNA interference (RNAi) strategies and CRISPR-Cas9 gene editing techniques are being developed to suppress or correct the mutated HTT gene at the DNA level. 1, 6
• Cell therapy strategies aim to replace lost neurons or provide trophic support to damaged brain regions, though these remain experimental. 1

Critical Pitfalls to Avoid

• Never overlook non-pharmacological approaches before initiating medication—this leads to suboptimal management. 1, 3
• Do not neglect personalized management that considers symptom variations, adverse drug reactions, potential complications, and drug interactions. 4, 1
• Recognize that tetrabenazine may cause functional decline: FDA trials showed decrements in activities of daily living scores compared to placebo. 2
• Remember that chorea scores return to baseline within one week of discontinuing tetrabenazine, indicating purely symptomatic benefit without disease modification. 2

Important Clinical Considerations

• Immunosuppressive therapies have no role in HD management, as the disease is not autoimmune but rather caused by direct neurotoxicity from mutant huntingtin protein. 7
• The disease mechanism involves toxic protein aggregation leading to progressive neurodegeneration over 15-20 years with no immune system involvement. 7
• Current treatments are purely symptomatic; no neuroprotective therapies exist that delay disease progression. 4, 7