What is the recommended management of Huntington disease?

Management of Huntington's Disease

Current Standard of Care: Symptomatic Management

The management of Huntington's disease focuses on pharmacological control of chorea and psychiatric symptoms, combined with structured non-pharmacological interventions, as there is currently no cure or disease-modifying therapy available in clinical practice. 1, 2

Pharmacological Management of Chorea

For chorea control, use deutetrabenazine (Austedo) or valbenazine (Ingrezza) as first-line agents, both FDA-approved specifically for Huntington's disease-associated chorea 2, 3:

• Deutetrabenazine is started at 6 mg daily and titrated weekly in 6 mg increments until chorea is controlled, side effects emerge, or a maximum dose of 48 mg daily is reached 3
• Clinical trials demonstrated a mean reduction of 4.4 units on the Total Maximal Chorea Score versus 1.9 units with placebo (treatment effect -2.5 units, p<0.0001) 3
• Tetrabenazine carries a black box warning for depression and suicidality and is contraindicated in actively suicidal patients or those with untreated depression 4

Antipsychotic medications serve dual purposes for patients with both chorea and psychiatric symptoms 1, 2, 5:

• Haloperidol, sulpiride, and quetiapine can manage chorea while simultaneously treating psychosis and severe behavioral disturbances 1, 5
• Start with low doses and titrate slowly ("start low, go slow") to minimize adverse effects 5

Management of Psychiatric Symptoms

Psychiatric manifestations require aggressive treatment as they are often highly responsive and represent a major source of disability 6, 7:

• Use antidepressants for depressive symptoms, which are common and increase suicide risk in this population 7, 8
• Employ mood stabilizers for affective instability 7
• Prescribe anxiolytics for anxiety symptoms 7
• Consider psychostimulants for apathy and cognitive slowing 7

Close monitoring for depression and suicidality is mandatory, particularly when initiating vesicular monoamine transporter 2 (VMAT2) inhibitors like tetrabenazine or deutetrabenazine 4:

• Patients, caregivers, and families must be educated about suicide risk and instructed to report concerning behaviors immediately 4
• Exercise particular caution in patients with prior depression, suicide attempts, or suicidal ideation 4

Non-Pharmacological Interventions

Implement structured environmental modifications before escalating pharmacological therapy 2, 5:

• Establish predictable daily routines with consistent timing for meals, activities, and sleep to reduce confusion and anxiety 2, 5
• Create a safe environment by removing hazards, installing safety locks, and reducing environmental stimuli that trigger agitation 2, 5
• Use the "three R's" approach: repeat, reassure, and redirect when managing behavioral disturbances 5
• Break complex tasks into simple steps with clear instructions for each component 5
• Employ visual cues, calendars, and labels to assist with orientation 5

Rehabilitation services should be continuously reassessed as the disease progresses 6, 7:

• Physical therapy maintains mobility and prevents falls 6, 7
• Occupational therapy preserves functional abilities and activities of daily living 6, 7
• Speech therapy addresses dysphagia and communication difficulties 6, 7
• Nutritional support becomes critical as weight loss progresses 7

Multidisciplinary Team Approach

Coordinate care through a multidisciplinary team including movement disorders specialists, genetic counselors, mental health professionals, physical therapists, and social workers 6, 7:

• Social work intervention assists with practical difficulties faced by patients and caregivers 6
• Genetic counseling is essential before DNA testing in symptomatic patients and mandatory for predictive testing in asymptomatic at-risk individuals 6
• Palliative care specialists should be involved as the disease advances 7, 9

Emerging Therapies (Not Yet Available for Clinical Use)

Gene-targeted therapies remain investigational and are not currently approved for clinical practice 1, 2:

• Antisense oligonucleotide (ASO) therapy showed initial promise with Tominersen reducing mutant huntingtin protein in cerebrospinal fluid, but the Phase III GENERATION HD1 trial was halted in March 2021 due to faster neurologic decline in the high-dose group compared to placebo 1
• Gene editing techniques, RNA interference strategies, and small molecule splicing modulators are in development but have not demonstrated clinical benefit 2
• Cell therapy strategies aimed at replacing lost neurons remain experimental 2

Critical Pitfalls to Avoid

Do not overlook non-pharmacological interventions before initiating medications, as environmental modifications can substantially reduce symptom burden without medication-related risks 2, 5

Avoid treating chorea aggressively if it does not limit function, as antichoreic medications carry significant risks including depression, parkinsonism, and sedation 7, 9:

• Focus therapy on symptoms that specifically impair daily activities 6
• Periodically reassess whether medication side effects contribute to disability as the disease progresses 6

Do not use multipurpose medications indiscriminately, but when appropriate, select agents that address multiple symptoms simultaneously to simplify regimens and improve compliance 7:

• For example, haloperidol can address chorea, agitation, and anorexia with a single agent 7

Recognize that patients typically lack insight into their disease manifestations and may resist treatment, requiring caregiver involvement in medication administration and monitoring 7