How to Target Psychiatric Symptoms of Huntington's Disease: Clinical Experience, Limited Evidence Guide Selection of Symptom-Focused Treatments

Psychiatric symptoms are a common and debilitating manifestation of Huntington's disease (HD), a progressive, inherited neurodegenerative disorder also characterized by chorea (involuntary, nonrepetitive movements) and cognitive decline. The prevalence of HD is 4 to 8 patients per 100,000 persons in most populations of European descent, with lower prevalence among non-Europeans. (1) HD is caused by an abnormal expansion of a trinucleotide (CAG) repeat sequence on chromosome 4, and is inherited in an autosomal dominant fashion, meaning a HD patient's child has a 50% chance of inheriting the mutation. The expansion is located in the gene that encodes the "huntingtin" protein, the normal function of which is not well understood. [ILLUSTRATION OMITTED] There's no cure for HD, and treatments primarily are directed at symptom control. Psychiatric symptoms include depression, apathy, anxiety, and psychosis (Table). (2-4) Treating patients with HD can be challenging because most psychiatrists will see only a handful of patients with this multifaceted illness during their careers. See this article at CurrentPsychiatry.com for a case study of a patient with HD. Table Psychiatric symptoms of HD Anxiety Apathy Delusions Disinhibitions, impulsivity, aggressive behavior Dysphoria Euphoria Hallucinations Irritability Obsessions and compulsions HD: Huntington's disease Source: References 2-4 Psychiatric sequelae In general, psychiatric symptoms of HD become increasingly prevalent over time (Box, page 37). (3), (5) In a 2001 study of 52 HD patients by Paulsen et al, (2) 51 patients had psychiatric symptom, such as dysphoria (69.2%), agitation (67.3%), irritability (65.4%), apathy (55.8%), and anxiety (51.9%); delusions (11.5%) and hallucinations (1.9%) were less prevalent. (2) Similarly, Thompson et al (3) followed 111 HD patients for [greater than or equal to]3 years and all experienced psychiatric symptoms. Box Psychiatric symptoms of HD change over time According to Thompson et a1, (3) the presence and severity of apathy, irritability, and depression trend differently across the course of Huntington's disease (HD). Apathy worsens with disease progression, closely following cognitive and motor symptoms. Irritability increases significantly, but this effect seems confined to early stages of HD. Depressive symptoms appear to decline slightly as HD advances, although it is unclear if this is because of antidepressants' effects, increasing emotional blunting, and waning insight in later stages of HD, or another unknown factor. (3) This study did not examine psychotic symptoms over time because few patients were experiencing delusions or hallucinations. Similar to Thompson et al, Naarding et al (5) found that apathy and depression in HD follow distinct time courses. Depression is a feature of early HD and apathy worsens with overall disease progression. Depressed mood and functional ability--not cognitive or motor symptoms (6)--are the 2 most critical factors linked to health-related quality of life in HD. Hamilton et al (7) found that apathy or executive dysfunction in HD patients is strongly related to decline in ability to complete activities of daily living, and may be severely debilitating. Apathy. Often mistaken for a symptom of depression, apathy's presentation may resemble anhedonia or fatigue; however, research suggests that depression and apathy are distinct conditions. Naarding et al (5) noted that apathy is more common than depressive symptoms in HD patients and may be a hallmark symptom of HD. Depression affects most HD patients, and often is most severe early in the disease course. Hubers et al (8) found that 20% of 100 HD patients had suicidal ideation. The strongest predictor was depressed mood. …