Irritability in Huntington’s Disease

Huntington’s disease (HD) is a heritable and fatal neurodegenerative disease characterized by a triad of motor, cognitive and neuropsychiatric symptoms. A common and particularly detrimental neuropsychiatric alteration in HD gene carriers is irritability, which frequently manifests as abrupt and unpredictable outbursts of anger. This symptom increases the burden of HD in multiple ways, such as jeopardizing employment and straining familial or caregiver support. Although irritability in HD is diagnosed by the administration of standardized rating scales and clinical expertise, measurement of severity and progression is complicated by several factors. Currently, individuals with HD who present with irritability may be managed with a variety of psychotropic medications, primarily antidepressants and antipsychotics. While these therapies offer relief to individuals suffering from irritability in HD, they are often not sufficient. Here, we review irritability in the context of HD and emphasize the need for treatments that are better tailored to mitigate this troublesome symptom. An expeditious strategy in pursuit of this goal involves evaluating the efficacy of approved medications that are used to treat similar neuropsychiatric symptoms.