Treatment algorithm

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

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all patients

1st line – counselling for patient and family, with carer support

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all patients
1st line – 

counselling for patient and family, with carer support

Almost all patients benefit from counselling about behavioural and genetic aspects of the illness and carer demands.

Counselling involves recognition of impulsivity, and safety advice regarding driving, use of firearms, and discarding accumulated prescription medicines.

Many families, having already dealt with an affected member, know a great deal about the effects of the illness. It is helpful to discuss variations in the disease. 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's disease support groups, and relevant governmental agencies can be of benefit. Acknowledging the challenges faced by carers should be part of every clinic visit.

A palliative care approach, integrated through the multidisciplinary team, is appropriate throughout the disease course for patients with Huntington's disease.[102][103] Wishes for end-of-life care and advance directives should be discussed with the patient and family/carers once they are ready to do so, before such care is needed, and should be an ongoing conversation.[102]

Consider – non-pharmacological interventions

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all patients
Consider – 

non-pharmacological interventions

Additional treatment recommended for SOME patients in selected patient group

Patients may benefit from non-pharmacological interventions, which can also be combined with pharmacological treatments.

The European Huntington’s Disease Network has published several best practice guidelines on the use of non-pharmacological interventions for Huntington's disease, such as occupational therapy, physiotherapy, speech and language therapy, and nutritional support.[98][99][100][101]

Home exercise programmes improve physical function in people with early to mid-stage Huntington's disease.[104]

Consider – tetrabenazine or antipsychotics or benzodiazepines or amantadine

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all patients
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with chorea but without prominent behavioural problems
Consider – 

tetrabenazine or antipsychotics or benzodiazepines or amantadine

Additional treatment recommended for SOME patients in selected patient group

When severe, chorea interferes with function; when mild, it contributes to social isolation.

Tetrabenazine and antipsychotics are the most efficacious medicines available.[61][84][85][86]

Adverse effects may aggravate underlying features of Huntington's disease. As such, these medicines should be reserved for situations in which chorea is problematic. Tetrabenazine should be avoided in patients with a history of psychiatric symptoms.

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; antichorea medicines should therefore be regularly reassessed and reduction considered.

Amantadine may improve chorea in Huntington's disease.[87][88][89][90][91]

Motor impersistence and abnormal eye movement, gait, speech, and coordination cannot be treated.

Primary options

tetrabenazine: 12.5 mg orally once daily initially, increase gradually according to response, maximum 200 mg/day

Secondary options

sulpiride: 100 mg orally twice daily initially, increase according to response, usual maintenance dose 200-600 mg/day

Tertiary options

risperidone: 0.5 mg orally once or twice daily initially, increase according to response, maximum 6 mg/day

OR

olanzapine: 2.5 mg orally at night initially, increase according to response, maximum 15-20 mg/day

OR

quetiapine: 25 mg orally daily initially, increase according to response, maximum 750 mg/day

OR

haloperidol: 0.5 to 1mg orally daily initially, increase according to response, maximum 6-8 mg/day

OR

clonazepam: 0.5 mg orally daily initially, increase according to response, maximum 4 mg/day

OR

diazepam: 1.25 mg orally daily initially, increase according to response, maximum 20 mg/day

OR

amantadine: 100 mg orally twice daily, maximum 300 mg/day

Consider – antidepressants

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all patients
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with depression
Consider – 

antidepressants

Additional treatment recommended for SOME patients in selected patient group

Generic selective serotonin reuptake inhibitors (SSRIs), such as citalopram, may be a reasonable first-line medicine. If the first medicine fails, patients should be tried on other antidepressants. Referral to a psychiatry consultant is appropriate, particularly for difficult cases.

A second option would be sertraline. More expensive agents, such as escitalopram, may also be considered.

If the patient is likely to be prescribed tetrabenazine, then citalopram, escitalopram, or sertraline are the preferred choices. The other SSRIs (fluoxetine, fluvoxamine, and paroxetine) inhibit CYP2D6 and may thus reduce clearance of tetrabenazine, causing toxic side effects.

In emergency or severe cases, drugs with a more rapid onset of action (e.g., mirtazapine) may be considered.[63]

Primary options

citalopram: 20 mg orally once daily for 2 weeks, followed by 40 mg once daily

OR

fluoxetine: 20 mg orally once daily initially, increase according to response every 2-4 weeks, maximum 60 mg/day

Secondary options

sertraline: 50 mg orally once daily for 1 week, followed by 100 mg once daily

OR

escitalopram: 10 mg orally once daily for 1 week, followed by 20 mg once daily

Tertiary options

mirtazapine: 15 mg orally once daily at bedtime for 1 week, followed by 30 mg once daily at bedtime for 1 week, increase further according to response, maximum 45 mg/day

Consider – mood-stabilising anticonvulsants

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all patients
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with behavioural problems and mood instability
Consider – 

mood-stabilising anticonvulsants

Additional treatment recommended for SOME patients in selected patient group

Standard approaches to managing temper and irritability include anticonvulsant agents with mood-stabilising properties (valproic acid and carbamazepine), benzodiazepines, and typical or atypical antipsychotic drugs.

Choosing among these agents is difficult in the absence of definitive studies.

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

In 2018, the European Medicines Agency recommended that valproate and its analogues are contraindicated during pregnancy due to the risk of congenital malformations and developmental problems in the infant/child.[78] In the US, standard practice is that valproate and its analogues are only prescribed during pregnancy if other alternative medications are not acceptable or not effective. In both Europe and the US, valproate medicines must not be used in female patients of childbearing potential unless there is a pregnancy prevention programme in place and certain conditions are met.[78]

Primary options

carbamazepine: 200 mg orally (extended-release) twice daily initially, increase to 400 mg twice daily according to response

OR

valproic acid: 750 mg/day orally given in 2-3 divided doses

Consider – selective serotonin reuptake inhibitors (SSRIs) or benzodiazepines

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all patients
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with behavioural problems where anxiety or insomnia is prominent
Consider – 

selective serotonin reuptake inhibitors (SSRIs) or benzodiazepines

Additional treatment recommended for SOME patients in selected patient group

Evidence is limited, but clinical experience suggests that treatment with SSRIs 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.

A benzodiazepine may be preferred in situations where anxiety or insomnia is more prominent.

Other approaches include anticonvulsant agents with mood-stabilising properties (valproic acid and carbamazepine), propranolol, and typical or atypical antipsychotic drugs. Choosing among these agents is difficult in the absence of definitive studies.

Primary options

citalopram: 20 mg orally once daily for 2 weeks, followed by 40 mg once daily

OR

clonazepam: 0.5 mg orally once daily at night initially, increase according to response, maximum 1 mg three times daily

Consider – selective serotonin reuptake inhibitors (SSRIs) or anxiolytics

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all patients
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with anxiety but without prominent behavioural problems
Consider – 

selective serotonin reuptake inhibitors (SSRIs) or anxiolytics

Additional treatment recommended for SOME patients in selected patient group

Anxiety may respond to an SSRI, such as citalopram, or to buspirone or traditional benzodiazepines, such as clonazepam.[70][71]

Primary options

citalopram: 20 mg orally once daily for 2 weeks, followed by 40 mg once daily

Secondary options

clonazepam: 0.5 mg orally once daily at night initially, increase according to response, maximum 1 mg three times daily

OR

buspirone: 5 mg orally three times daily for 2 weeks, followed by 10 mg twice daily

Consider – selective serotonin reuptake inhibitors (SSRIs) or antipsychotics or clomipramine and/or cognitive behavioural therapy (CBT)

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all patients
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with obsessive-compulsive behaviours and perseveration
Consider – 

selective serotonin reuptake inhibitors (SSRIs) or antipsychotics or clomipramine and/or cognitive behavioural therapy (CBT)

Additional 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.[72][73] Longer-duration and higher-dose therapy may be needed. Given the problematic nature of such symptoms in some patients, persistence is warranted.

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

Obsessive and compulsive symptoms are sometimes responsive to antipsychotic medicine. Olanzapine may be effective.[74][75] Antipsychotic agents 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 medicines. It may also be of benefit in Huntington's disease, particularly in patients without significant cognitive impairment.

Primary options

citalopram: 20 mg orally once daily for 2 weeks, followed by 40 mg once daily

OR

fluoxetine: 20 mg orally once daily initially, increase according to response every 2-4 weeks, maximum 60 mg/day

OR

olanzapine: 5 mg orally once daily for 1 week, followed by 10 mg once daily

Secondary options

clomipramine: 25 mg orally once daily initially, gradually increase to 100 mg/day given in divided doses over 2 weeks, maximum 250 mg/day

Consider – antipsychotics

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all patients
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with behavioural problems and chorea or bradykinesia/rigidity, weight loss, or need for acute management
Consider – 

antipsychotics

Additional treatment recommended for SOME patients in selected patient group

Standard approaches to managing temper and irritability include anticonvulsant agents with mood-stabilising properties (valproic acid and carbamazepine), benzodiazepines, and typical or atypical antipsychotic drugs.

Choosing among these agents is difficult in the absence of definitive studies.

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

For patients with co-existent significant chorea, typical (first-generation) antipsychotics (e.g., haloperidol) may be helpful. Sulpiride can also be used.

Atypical antipsychotics (e.g., quetiapine, olanzapine) are more appropriate for people with co-existent bradykinesia and rigidity.

Given the adverse effects of antipsychotic medicines, occasional dose reductions or holidays are appropriate.

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

Primary options

haloperidol: 0.5 mg orally twice daily initially, increase according to response, maximum 6 mg/day, consider downwards titration at 3-6 month intervals

OR

quetiapine: 25 mg orally (immediate-release) twice daily initially, increase according to response, maximum 450 mg/day

OR

olanzapine: 5 mg orally once daily for 1 week, followed by 10 mg once daily

Secondary options

sulpiride: 100 mg orally twice daily initially, increase according to response, usual maintenance dose 200-600 mg/day

Consider – dopamine agonists

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all patients
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bradykinesia and rigidity predominant without prominent behavioural problems
Consider – 

dopamine agonists

Additional treatment recommended for SOME patients in selected patient group

In general, such symptoms are difficult to treat.[92][93][94] Carbidopa/levodopa could be tried. 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.

Primary options

carbidopa/levodopa: 25/100 mg orally (immediate-release) three times daily for 1-2 weeks, increase according to response, maximum 200/800 mg per day

OR

amantadine: 100 mg orally twice daily, maximum 300 mg/day

Consider – electroconvulsive therapy (ECT)

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all patients
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with depression refractory to drugs
Consider – 

electroconvulsive therapy (ECT)

Additional 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's disease.[66][67][68][69]

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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

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