Huntington disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

all patients

1st line – counseling for patient and family with caregiver support

Back

1st line –

counseling for patient and family with caregiver support

Soon after the genetic diagnosis and at various time points along the course of their journey, discussion with patients and family members should address the hereditary nature of the disease, its natural history including variations in speed of progression/sequence of events, behavioral issues, as well as provide safety advice regarding driving, use of firearms, and discarding accumulated prescription drugs. Huntington disease can significantly affect family dynamics, often driven by behavioral symptoms, its hereditary nature, as well as the demands placed on caregivers. If there has been a particularly problematic experience in the family, such information can be comforting.

The burden of caring for an affected patient is considerable and it taxes families emotionally, physically, and financially. Directing families to community resources, Huntington disease support groups, and relevant governmental agencies can be of benefit. Huntington's Disease Society of America Opens in new window International Huntington Association Opens in new window Acknowledging the challenges faced by caregivers should be part of every clinic visit.

Advance care planning discussion can be helpful at any point in the course of the disease and should form a regular component of clinical review, tailored according to whether the patient is ready and willing to engage in the conversation.[102] Topics may include wishes for end-of-life care, appointment of lasting power of attorneys, advance decision to refuse treatment, and advance statements.[102][103]

A palliative care approach, integrated through the multidisciplinary team, is appropriate throughout the disease course for patients with Huntington disease to address symptoms that are difficult to treat.[103][104]

Consider – nonpharmacologic supportive interventions

Back

Consider –

nonpharmacologic supportive interventions

Treatment recommended for SOME patients in selected patient group

Patients usually benefit from multidisciplinary care, with a combination of pharmacologic and nonpharmacologic treatments.

Refer patients for appropriate nonpharmacologic care. There is evidence that physical therapy interventions can improve fitness, motor function, and gait in people with Huntington disease.[96] Home exercise programs improve physical function in people with early- to mid-stage Huntington disease.[97] Speech therapy and swallowing therapy have not been tested rigorously in Huntington disease but may be of transient benefit.

The European Huntington’s Disease Network has published several best practice guidelines on the use of nonpharmacologic interventions for Huntington disease, such as occupational therapy, physical therapy, speech and language therapy, and nutritional support.[98][99][100][101] EHDN: physiotherapy working group Opens in new window

A driving assessment by an independent assessor can be helpful in deciding whether driving remains safe.

with chorea but without prominent behavioral problems

Consider – tetrabenazine or antipsychotic

Back

Consider –

tetrabenazine or antipsychotic

Treatment recommended for SOME patients in selected patient group

Establish whether the patient feels affected by chorea prior to commencing any therapy. When severe, chorea interferes with function and ability to receive personal care; when mild, it can contribute to social isolation, but it varies from one individual to another.[63][80]

Treatment options for chorea include tetrabenazine or an atypical antipsychotic.

Tetrabenazine is a selective reversible vesicular monoamine transport 2 (VMAT2) inhibitor. Clinical trials have shown that tetrabenazine significantly reduces chorea.[64][83][84][85] Tetrabenazine has a shorter latency to effect and offset from the institution of therapy compared with antipsychotics, and it is free of any concerns of tardive dyskinesia. However, it is more likely to cause depression and sedation.[83] Patients with chorea in whom it is perceived as a significant problem are suitable candidates for treatment with tetrabenazine, particularly those who cannot tolerate antipsychotics. It is a good first-line choice for patients in whom chorea alone needs management (i.e., patients who do not need the adverse effects of weight gain or night sedation and/or management of irritation or agitation).

Antipsychotics are among the most effective drugs available for this indication. Atypical antipsychotics (e.g., olanzapine, risperidone) are the preferred drugs in clinical practice because of their improved adverse-effect profile compared with first-generation antipsychotics.[86]

Adverse effects may aggravate underlying features of Huntington disease. As such, these drugs should be reserved for situations in which chorea is problematic for the patient.

Tetrabenazine should be avoided in patients with a history of severe depressive symptoms and suicidality/ideation. It is contraindicated in patients with active suicidality or untreated or inadequately treated depression. Monitor patients on treatment for new or worsening depression or suicidality. Significant drug-drug interactions exist with tetrabenazine, in particular CYP2D6 inhibitors (e.g., certain selective serotonin-reuptake inhibitors [SSRIs] which may be used to treat other symptoms in patients with Huntington disease), and you should consult a drug interaction database before prescribing this drug.

The natural history of the movement disorder is such that in later stages of the disease, chorea tends to decline, and bradykinesia and rigidity increase; drug treatments should therefore be regularly reassessed and reduction considered.

Primary options

tetrabenazine: 12.5 mg orally once daily in the morning for 1 week, followed by 12.5 mg twice daily for 1 week, then may increase by 12.5 mg/day at weekly intervals, maximum 50 mg/day

Secondary options

olanzapine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10-30 mg/day

risperidone: 0.5 to 2 mg/day orally given in 1-2 divided doses initially, increase gradually according to response, maximum 10 mg/day

with depression

Consider – antidepressant and/or cognitive behavioral therapy (CBT)

Back

Consider –

antidepressant and/or cognitive behavioral therapy (CBT)

Treatment recommended for SOME patients in selected patient group

Treatment of depression is vital and reduces the risk of suicide. First-line treatments are antidepressants and/or CBT.[63]

Comparative studies of antidepressants in Huntington disease are not available, so choice of agents is based on clinical judgment relating to likely benefit and harms, suicide potential from overdose, and associated behavioral symptoms. Selective serotonin-reuptake inhibitors (SSRIs; e.g., citalopram, sertraline, escitalopram) are most commonly used.[63] Citalopram is frequently used as a first-line choice for patients with depression alone, and sertraline is often used first-line for patients with depression and comorbid irritability or anxiety. Second-line options include escitalopram.

If the patient is likely to be prescribed tetrabenazine, then citalopram, sertraline, or escitalopram are the preferred choices. Other SSRIs (fluoxetine, fluvoxamine, paroxetine) are more potent inhibitors of CYP2D6 and may thus reduce clearance of tetrabenazine, causing toxic adverse effects.

In emergency or severe cases, drugs with a more rapid onset of action (e.g., mirtazapine, a tetracyclic antidepressant) may be considered.[66] Mirtazapine can also be helpful if there is concomitant insomnia.[32]

If there are adverse events or failure of response to any drug, trial another drug or consider referral to a psychiatrist.

Psychotherapy (e.g., CBT) and counseling can be extremely helpful for patients with Huntington disease experiencing depressive symptoms. While only small, uncontrolled studies are available to support the use of psychotherapy for depression in patients with Huntington disease, guidelines suggest considering it based on evidence from other neurodegenerative diseases and the general population.[63][69][70]

Suicidality should be proactively explored and assessed on a regular basis.

Primary options

citalopram: 20-40 mg orally once daily

sertraline: 50-200 mg orally once daily

Secondary options

escitalopram: 10-20 mg orally once daily

mirtazapine: 15-45 mg orally once daily at bedtime

with behavioral problems and mood instability

Consider – atypical antipsychotic or mood-stabilizing anticonvulsant

Back

Consider –

atypical antipsychotic or mood-stabilizing anticonvulsant

Treatment recommended for SOME patients in selected patient group

Guidelines recommend considering environmental causes and behavioral strategies to reduce irritability before initiating pharmacologic treatment.[63] This may include reducing noise and other sources of overstimulation; addressing pain or other physical sources of discomfort; and instituting regular, structured routines where possible. Psychoeducation for the patient’s family on strategies to help avoid confrontation may also be beneficial.[32][63]

Choosing among the pharmacologic options for managing temper and irritability is difficult in the absence of definitive studies. Standard approaches include atypical antipsychotics (e.g., olanzapine, quetiapine) or anticonvulsants with mood-stabilizing properties (e.g., valproic acid).

Antipsychotics have been used with success in managing irritability and aggression; however, few published studies are available for specific guidance.[36][79] The choice of antipsychotic is based on adverse-effect profile. Given the adverse effects of antipsychotics, regular monitoring is essential, and occasional dose reductions or drug holidays are appropriate. Review for effectiveness after 4 weeks of treatment.

Valproic acid may be more suitable in situations where symptoms are just emerging or where sedating adverse effects are of concern.

Primary options

olanzapine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10-20 mg/day

quetiapine: 25 mg orally (immediate-release) once daily at bedtime initially, increase gradually according to response, maximum 750 mg/day given in 2-3 divided doses

valproic acid: 250-500 mg orally three times daily initially, increase gradually according to response, maximum 60 mg/kg/day

with behavioral problems where anxiety or insomnia is prominent

Consider – selective serotonin-reuptake inhibitor (SSRI) or benzodiazepine and/or cognitive behavioral therapy (CBT)

Back

Consider –

selective serotonin-reuptake inhibitor (SSRI) or benzodiazepine and/or cognitive behavioral therapy (CBT)

Treatment recommended for SOME patients in selected patient group

Choosing among the pharmacologic options for managing temper and irritability is difficult in the absence of definitive studies.

Evidence is limited, but clinical experience suggests that treatment with SSRIs such as citalopram is often effective, especially in the earlier stages; doses at the upper end of the manufacturer’s recommended range are usually necessary for this indication.[63]

A benzodiazepine (e.g., clonazepam) may be preferred in situations where anxiety or insomnia is more prominent. However, benzodiazepines may have a disinhibiting effect in some patients.

Psychotherapy can be helpful and complementary to pharmacologic intervention for anxiety.[32]

Primary options

citalopram: 20-40 mg orally once daily

clonazepam: 0.25 mg orally twice daily initially, increase according to response, maximum 4 mg/day

with anxiety but without prominent behavioral problems

Consider – selective serotonin-reuptake inhibitor (SSRI) or anxiolytic and/or cognitive behavioral therapy (CBT)

Back

Consider –

selective serotonin-reuptake inhibitor (SSRI) or anxiolytic and/or cognitive behavioral therapy (CBT)

Treatment recommended for SOME patients in selected patient group

Anxiety may respond to an SSRI, such as citalopram, or traditional benzodiazepines, such as clonazepam.

Psychotherapy (e.g., CBT) can be helpful and complementary to pharmacologic intervention.[32]

Primary options

citalopram: 20-40 mg orally once daily

Secondary options

clonazepam: 0.25 mg orally twice daily initially, increase gradually according to response, maximum 4 mg/day

with obsessive-compulsive behaviors and perseveration

Consider – selective serotonin-reuptake inhibitor (SSRI) or antipsychotic or clomipramine and/or cognitive behavioral therapy (CBT)

Back

Consider –

selective serotonin-reuptake inhibitor (SSRI) or antipsychotic or clomipramine and/or cognitive behavioral therapy (CBT)

Treatment recommended for SOME patients in selected patient group

SSRIs, such as citalopram or fluoxetine, may have a role in the management of obsessive-compulsive symptoms.[73][74] Longer-duration and higher-dose therapy may be needed for this indication, under specialist supervision. Given the problematic nature of such symptoms in some patients, persistence is warranted.

Clomipramine (a tricyclic antidepressant) has a higher incidence of adverse events but may be considered if fluoxetine fails.

Obsessive and compulsive symptoms are sometimes responsive to antipsychotics. Olanzapine may be effective.[75][76]

Antipsychotics are more likely to be helpful in patients with problematic chorea and agitation; antidepressants are helpful in patients with apathy.

CBT is also effective in the general population for obsessions and compulsions, either alone or in combination with drug therapy. It may also be of benefit in Huntington disease, particularly in patients without significant cognitive impairment.[63]

As dementia progresses, the obsessions often remit, perhaps because the patient becomes less able to retain the obsession in active memory. Psychiatric referral may be of benefit.

Primary options

citalopram: 20 mg orally once daily initially, increase gradually according to response, maximum 60 mg/day

fluoxetine: 20 mg orally once daily initially, increase gradually according to response, maximum 80 mg/day

olanzapine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day

Secondary options

clomipramine: 25 mg orally once daily initially, increase gradually according to response, maximum 250 mg/day

with behavioral problems and chorea or bradykinesia/rigidity, weight loss, or need for acute management

Consider – antipsychotic

Back

Consider –

antipsychotic

Treatment recommended for SOME patients in selected patient group

Choosing among the pharmacologic options for managing temper and irritability is difficult in the absence of definitive studies.

Antipsychotics may be more suitable in circumstances where weight loss and chorea are prominent and symptoms need more acute management.

Atypical antipsychotics (e.g., quetiapine, olanzapine) can also be helpful if there is coexistent involuntary movements and/or bradykinesia and rigidity.

The choice of antipsychotic is based on adverse-effect profile. Given the adverse effects of antipsychotics, regular monitoring is essential, and occasional dose reductions or drug holidays are appropriate.

Higher starting doses, or parenteral doses, of antipsychotics can be considered for acute, severe behavior problems. Olanzapine may also be administered parenterally if needed.

Primary options

olanzapine: 2.5 mg orally once daily initially, increase gradually according to response, maximum 10-20 mg/day; 10 mg intramuscularly as a single dose, may repeat 2 hours after initial dose and 4 hours after second dose if required, maximum 30 mg/day

quetiapine: 25 mg orally (immediate-release) once daily at bedtime initially, increase gradually according to response, maximum 750 mg/day given in 2-3 divided doses

bradykinesia and rigidity predominant without prominent behavioral problems

Consider – dopamine agonist

Back

Consider –

dopamine agonist

Treatment recommended for SOME patients in selected patient group

In general, such symptoms are difficult to treat.[91][92][93] Carbidopa/levodopa could be tried.[63] A response should be apparent by 1 month, otherwise discontinue.

A therapeutic response with amantadine should be apparent at the end of the third week; discontinue if there is no therapeutic response by this time.[87]

Primary options

carbidopa/levodopa: 10/100 mg orally (immediate-release) three to four times daily or 25/100 mg three times daily initially, increase gradually according to response, maximum 200/2000 mg/day

amantadine: 100 mg orally twice daily, increase gradually according to response, maximum 300 mg/day

with depression refractory to drugs

Consider – electroconvulsive therapy (ECT)

Back

Consider –

electroconvulsive therapy (ECT)

Treatment recommended for SOME patients in selected patient group

In patients with refractory depression, ECT can be of significant benefit. ECT has not been found to aggravate other aspects of Huntington disease.[71][72]

Use of this content is subject to our disclaimer

Huntington disease

Treatment algorithm

all patients

counseling for patient and family with caregiver support

nonpharmacologic supportive interventions

tetrabenazine or antipsychotic

Primary options

Secondary options

antidepressant and/or cognitive behavioral therapy (CBT)

Primary options

Secondary options

atypical antipsychotic or mood-stabilizing anticonvulsant

Primary options

selective serotonin-reuptake inhibitor (SSRI) or benzodiazepine and/or cognitive behavioral therapy (CBT)

Primary options

selective serotonin-reuptake inhibitor (SSRI) or anxiolytic and/or cognitive behavioral therapy (CBT)

Primary options

Secondary options

selective serotonin-reuptake inhibitor (SSRI) or antipsychotic or clomipramine and/or cognitive behavioral therapy (CBT)

Primary options

Secondary options

antipsychotic

Primary options

dopamine agonist

Primary options

electroconvulsive therapy (ECT)