The psychopharmacology of Huntington disease

Huntington disease (HD) is a hereditary neurodegenerative disorder caused by an expanded cytosine-adenine-guanine triplet repeat in the huntingtin gene. The current diagnosis is based on the presence of typical motor signs in combination with a positive gene test. The motor onset of the disease is usually between 30 and 50 years of age, and the disease then progresses over around 20 more years. Nonmotor symptoms and signs such as cognitive decline, metabolic dysfunction, sleep disturbances, as well as psychiatric symptoms are common and can occur many years before motor onset. Psychiatric symptoms include irritability, apathy, depression, anxiety, and OCD. Although there exist no disease-modifying treatment, available pharmacologic drugs often offer significant symptom relief and improve quality of life. Today, there are only two drugs that are approved by the US Food and Drug Association for the treatment of HD. These are the dopamine-depleting drugs tetrabenazine and deutetrabenazine that both target motor symptoms. The current status of best clinical practice for HD is based on expert opinions as well as evidence and/or experience of treating similar symptoms in other conditions. In this chapter, we provide an overview of the complex clinical manifestations of HD and the commonly used psychopharmacologic treatments.