Surgical Care
Ablative surgical procedures and fetal cell transplantation have been attempted in patients with HD. Currently, enough data to support this type of treatment are not available. It is still experimental.
Approach Consideration
Consider general safety measures and nonpharmacologic interventions first in the management of Huntington disease (HD).
If chorea is severe enough to interfere with function, consider treatment with benzodiazepines, such as clonazepam or diazepam; valproic acid; dopamine-depleting agents (eg, reserpine, tetrabenazinem deutetrabenazine); and finally, neuroleptics.
The drug tetrabenazine, a central acting vesicular monoamine transporter 2 (VMAT2) inhibitor, has shown positive effects in the treatment of chorea, for patients with HD. It selectively depletes central monoamines by reversibly binding to VMAT2.
Results from a phase III clinical study showed that this investigational drug is an effective treatment for chorea associated with HD. The dosing range that proved effective was 12.5-100 mg/d. [16] Its manufacturer has been granted fast track and orphan drug status by the FDA. It was the first treatment approved for chorea in patients with HD in the United States. Always weigh potential adverse effects against the benefits of each drug.
A second VMAT2 inhibitor, deutetrabenazine, was approved by the FDA in April 2017. Approval was based on a double-blind multicenter trial conducted in 90 ambulatory patients at 34 centers in the United States and Canada, with 45 patients randomly assigned to deutetrabenazine and 45 to placebo. Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout.
Baseline total maximal chorea score was 8 or higher in study participants. Results showed improvement in the Unified Huntington Disease Rating Scale total maximal chorea scores for patients taking deutetrabenazine of 4.4 units from baseline to the maintenance period (average of week 9 and week 12), compared with approximately 1.9 units for patients taking placebo. The treatment effect of –2.5 units was statistically significant (P < .0001). [17]
Patients who have HD and predominant features of bradykinesia and rigidity may benefit from treatment with levodopa or dopamine agonists. [18]
Depression in patients with HD is treatable and should be recognized promptly. Selective serotonin reuptake inhibitors (SSRIs) should be considered as first-line therapy. Other antidepressants, including bupropion, venlafaxine, nefazodone, and tricyclic antidepressants, also can be used. Electroconvulsive therapy (ECT) can be used in patients with refractory depression.
Antipsychotic medications may be necessary in patients with hallucinations, delusions, or schizophrenia-like syndromes. Newer agents, such as quetiapine, clozapine, olanzapine, and risperidone, are preferred to older agents because of the lower incidence of extrapyramidal side effects and the decreased risk for tardive syndromes.
Irritability may be treated with antidepressants, particularly the SSRIs; mood stabilizers, such as valproic acid or carbamazepine; and, if needed, atypical neuroleptics.
Other less frequent aspects of HD that may require pharmacologic treatment are mania, obsessive-compulsive disorder, anxiety, sexual disorders, myoclonus, tics, dystonia, and epilepsy.
