Managing the Many Psychiatric Sides of Huntington’s Disease

Though Huntington’s disease (HD) is commonly thought of as an inherited neurological disorder, changes in mood and behavior are a central feature of HD symptomology. Patients with HD will usually exhibit multiple neuropsychiatric symptoms during illness progression, which can be attributed to both the neurodegeneration of brain cells and the psychological stress of living with a chronic disease. Medications commonly used to manage HD motor problems like chorea (involuntary movements) can also have psychiatric side effects.

Because HD is rare, most psychiatrists may not be familiar with treating patients who have it. I recently participated on an expert panel that developed a set of consensus guidelines for five HD neuropsychiatric symptoms—agitation, anxiety, apathy, psychosis, and sleep disorders—that offers recommendations.

Of these five categories, the latter three warrant additional attention because their management requires special considerations for patients with HD. For example, when diagnosing apathy, be aware that the neurological damage of HD contributes to slower cognition, speech latency, and delays in initiating movement that might be mistaken for a lack of interest or initiative. Treating HD-related apathy is best done by encouraging social and physical activities adapted to the patient’s interests and physical abilities, along with a dose reduction of medications prescribed for other symptoms (like depression or anxiety) if possible, since they may worsen apathy. For non-depressed HD patients with apathy, you can also consider a trial with a stimulant medication or an activating antidepressant (one with stimulant-like properties).

Psychotic symptoms such as delusions and hallucinations can be difficult to diagnose. Some patients exhibit low-level or transient psychosis during the early part of HD, and as HD progresses, cognitive and speech impairments may mask more pronounced psychotic symptoms. Patients with HD also exhibit perseveration (repeating words or gestures without any stimulus), which can be mistaken for delusional behavior or a symptom of obsessive-compulsive disorder.

The consensus among our HD experts is that second-generation antipsychotics are a preferred treatment for psychotic symptoms, but first-generation antipsychotics may be used in patients with significant chorea. When choosing a type and dose of antipsychotic, focus on limiting unwanted side effects such as apathy. The emerging side effects of an antipsychotic, such as akathisia or tardive dyskinesia, may be difficult to distinguish from the natural progression of HD symptoms. It is therefore important to carefully and regularly reassess the need for antipsychotics in all patients receiving them.

That need for continual reevaluation holds true when treating sleep disorders, which are a more common neuropsychiatric HD symptom. Hypnotic drugs are associated with side effects that include fatigue, apathy, slowed thinking, and difficulties with balance—all hallmarks of HD progression. Given that several behavioral treatments to improve sleep hygiene are available, these should be considered first when treating a sleep disorder.

If behavioral options are insufficient, medications may be needed. Patients who show a pattern of circadian rhythm disruption may be given melatonin, whereas sedating antidepressants (for example, mirtazapine) or antipsychotics (for example, quetiapine) are options for other types of sleep disorders. Selection should be based on side-effect profile as well as the presence of coexisting problems like depression or agitation. Clomipramine is also a pharmacologic option for sleep if a patient has co-occurring perseveration or obsessive symptoms. Benzodiazepines should be avoided, if possible, in ambulatory patients because of the increased risk of falls.

As can be seen above, a few common themes emerge when assessing HD neuropsychiatric symptoms. One is that polypharmacy should be avoided as much as possible because neuropsychiatric medications have side effects that resemble natural HD symptoms, which makes monitoring disease progression difficult. Behavioral therapies should be tried first when possible, to be supplemented with medications that cover a broad range of symptoms and have favorable safety profiles. Because HD is a progressive disorder, treatment strategy will continually change, so each patient’s behavioral and cognitive state should be assessed regularly.

Finally, it is critical to educate patients and their caregivers about the range of neuropsychiatric symptoms in HD and the treatments that are available for all these symptoms. This information can help build the therapeutic alliance and improve symptom reporting. ■