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 al8 found that 20% of 100 HD patients had suicidal ideation. The strongest predictor was depressed mood.
Sleep disturbances and daytime somnolence are common among HD patients, and patients with comorbid depression report more disturbed sleep. Managing disturbed sleep and daytime somnolence in HD, with emphasis on comorbid depression, may improve the quality of life of patients and their caregivers.9
Anxiety was present in >50% of HD patients in a study by Paulsen et al2 and 37% evaluated by Craufurd et al.10 Craufurd et al10 also reported that 61% of patients were “physically tense and unable to relax.”
Among HD patients, 5% report obsessions and 10% report compulsive behaviors; these symptoms appear to become increasingly common as HD progresses.4,10
Impulsivity and disinhibition. Craufurd et al10 found that 71% of HD patients experienced poor judgment and self-monitoring, 40% had poor temper control and verbal outbursts, 22% exhibited threatening behavior or violence, and 6% had disinhibited or inappropriate sexual behavior.10
Recent studies have shown higher rates of disinhibition in “presymptomatic” gene-positive subjects vs gene-negative controls, suggesting that these symptoms may arise early in HD.11 Further, researchers demonstrated that patients lack symptom awareness and rate themselves as less impaired than their caregivers do.11
In our clinical experience, impulsivity frequently is encountered and creates significant conflict between patients and their caregivers. We speculate that when coupled with depressive symptoms of HD, impulsivity and disinhibition may play an important role in the high rates of suicidality seen in these patients.
Psychosis. Delusions and hallucinations are less common in HD than other psychiatric symptoms. Craufurd et al10 reported 3% of HD patients had delusions, 3% had auditory hallucinations, 2% had tactile hallucinations, and no patients had visual hallucinations.
A few case reports and a small study by Tsuang et al12 suggested that psychotic features in HD may be similar to those seen in paranoid schizophrenia. Tsuang et al12 also noted that more severe HD-related psychosis tends to cluster in families, which suggests that susceptibility to HD psychosis may be heritable.
Treating psychiatric symptoms
High-quality randomized controlled trials of pharmacotherapies for psychiatric symptoms in HD patients are lacking. Decisions regarding which agents to use often are based on case reports or clinical experience. The suggestions below are based on available evidence and our clinical experience.
Depression. Depressive symptoms in HD seem to respond to conventional pharmacologic treatments for major depressive disorder (MDD). A small trial of venlafaxine extended-release (XR) in 26 HD patients with MDD showed statistically significant improvements in depressive symptoms; however, this trial was not blinded and did not have a placebo group.13 In addition, 1 in 5 patients developed significant side effects—nausea, irritability, or worsening chorea.13
Evidence for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants (TCAs) is lacking. Antidepressant choice should be based on patient response, side effect profile, and the need for secondary therapeutic effects.14
We often prescribe sertraline, citalopram, or escitalopram for our HD patients because of the relative absence of drug-drug interactions and favorable safety profile in medically and surgically ill patients. However, it’s important to tailor the treatment approach to your patient’s needs—eg, patients prone to forgetting their medicine may benefit from a drug with a longer half-life, such as fluoxetine. We avoid TCAs because of their anticholinergic effects, which may worsen dementia symptoms. Because HD patients have high rates of suicidality, agents that are highly toxic when taken in overdose should be used with caution.
One small study of HD patients with MDD or bipolar disorder showed clinical improvement in depressive symptoms after electroconvulsive therapy (ECT).15 Patients who suffered from comorbid delusions had the best improvements in mood.15 ECT likely is a good choice for HD patients who have failed several antidepressants, are suicidal, or who have depression with psychotic features.16
Apathy. A 2011 review concluded that no evidence-based recommendations regarding pharmacologic treatment for apathy in HD can be made because of lack of research.7 The Huntington’s Disease Society of America’s (HDSA) A Physician’s Guide to Managing Huntington’s Disease includes recommendations for treating apathy based on clinical experience.16 It suggests a nonsedating SSRI, followed by a trial of methylphenidate, pemoline, or dextroamphetamine if SSRIs were unsuccessful.