Current and Emerging Strategies for Managing Huntington Disease Symptoms: Karen Anderson, MD

Huntington disease (HD) is a progressive, inherited neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms that can significantly affect daily functioning and quality of life. Although chorea is among the most recognizable manifestations of the disease, patients frequently experience cognitive impairment, apathy, depression, irritability, and other behavioral symptoms that may emerge years before motor abnormalities become apparent. As research into disease-modifying therapies continues to advance, optimizing the management of these diverse symptoms remains a critical component of patient care.

At the 2026 Advanced Therapeutics in Movement & Related Disorders (ATMRD) Congress, held June 5-7 in Washington, D.C., experts discussed evolving approaches to the treatment of HD and other movement disorders. Among the featured presentations was a session led by Karen Anderson, MD, professor of psychiatry and neurology at Georgetown University. The session focused on the neurologic, cognitive, and psychiatric manifestations of HD, including practical strategies for symptom management and emerging therapeutic developments.

In an interview with NeurologyLive®, Anderson discussed current approaches to managing the neurologic, cognitive, and psychiatric manifestations of HD. The conversation also explored the often-underrecognized cognitive symptoms of the disease while addressing ongoing treatment challenges, including the risk of undertreating motor symptoms and the limited evidence-based options for cognitive impairment.

NeurologyLive: Can you provide an overview of your talk and the key takeaways for clinicians?

Karen Anderson, MD: We had a discussion about the treatment of neurologic, cognitive, and psychiatric symptoms in HD. Starting with neurologic symptoms, we talked about how VMAT2 inhibitors—including tetrabenazine, deutetrabenazine, and valbenazine—are extremely useful for suppressing chorea, which can improve both quality of life and day-to-day functioning for patients.

We then discussed cognitive symptoms in HDand how they can occur much earlier than the motor symptoms. In fact, cognitive impairment can be one of the main reasons patients stop working. Much of this relates to executive dysfunction. Patients often have difficulty switching between tasks, staying on task, organizing their time, and focusing their attention appropriately.

Sometimes we use medications approved for Alzheimer disease, such as donepezil or rivastigmine, off-label to address cognitive symptoms, although we do not have definitive evidence that these therapies are effective in HD. My primary focus, however, was on the behavioral and psychiatric manifestations of the disease.

People with HDcan experience any psychiatric symptom seen in the general population, but some symptoms appear to be more common because of disruptions in the circuitry connecting the basal ganglia and frontal cortex. Obsessive-compulsive symptoms, for example, are frequently observed. I spent considerable time discussing apathy, which is a disorder of motivation characterized by difficulty initiating activities, becoming engaged, and maintaining interest in everyday tasks.

What are some of the most important considerations when managing psychiatric symptoms in HD?

For apathy, we discussed several behavioral strategies that can be very helpful. Structuring a patient's day, providing external support, and having someone perform activities alongside the patient rather than simply assigning tasks can make a meaningful difference. We also reviewed medication strategies, including identifying and reducing medications that may worsen apathy.

For example, if a VMAT2 inhibitor is prescribed at too high a dose, a patient may appear apathetic. Antipsychotics and even SSRI antidepressants can contribute as well. In some cases, we may consider activating antidepressants such as bupropion or even low-dose stimulants like methylphenidate. However, clinicians need to be cautious because stimulating medications can sometimes worsen irritability.

I also discussed irritability and aggression, which can become major clinical concerns. Irritability is often an internal feeling of anger or frustration, whereas aggression represents the behavioral manifestation of those feelings. Patients frequently have limited insight and may perceive others as the problem rather than recognizing their own heightened sensitivity.

When irritability progresses to aggression, the consequences can be significant, including property destruction, harm to pets, or injury to family members. Because of this, we treat these symptoms aggressively once they emerge. If someone is irritable but not aggressive, I will often start with an antidepressant, typically one with more sedating properties, such as escitalopram. If aggression is already present, I am more likely to use an antipsychotic medication such as olanzapine, quetiapine, or risperidone.

Are there any technologies that may help patients manage symptoms such as apathy?

For apathy, technology can be useful when it helps provide structure and external motivation. For example, wearable devices or smartphone reminders can prompt patients to exercise or complete activities throughout the day. Some patients benefit from seeing measurable goals, such as step counts, which can provide motivation to stay active.

Technology is somewhat less helpful for irritability and aggression, although it may provide opportunities for engagement and distraction. Finding activities or content that patients find meaningful and enjoyable can sometimes reduce frustration and improve quality of life.

What are some of the ongoing challenges in treating HD?

One concern I have is that motor symptoms are often undertreated. Many clinicians who are not HD specialists have limited experience with VMAT2 inhibitors. As a result, they may start at a low dose and never increase it, even when chorea remains inadequately controlled.

There is no single target dose for these medications, and patients do not need to be pushed to the maximum dose. However, treatment should be titrated until chorea is adequately suppressed without causing side effects such as depression, anxiety, sedation, suicidal thinking, or parkinsonism.

Another challenge is the lack of highly effective treatments for cognitive symptoms. We do not have strong evidence-based therapies in this area. I also spend a considerable amount of time evaluating whether medications such as high-dose antipsychotics or benzodiazepines may be contributing to cognitive impairment and determining whether those medications can be reduced.

When it comes to psychiatric symptoms, treatment is often similar to what we would do in general psychiatry. Patients do not necessarily need a HD diagnosis to receive treatment for depression, anxiety, or other psychiatric conditions. If someone is depressed, they should be treated appropriately regardless of the underlying neurologic diagnosis.

Looking ahead, where do you see the field heading in the future?

We are incredibly fortunate to be at a moment when we finally have therapies capable of lowering huntingtin protein, which is the abnormal protein responsible for HD. Everyone has huntingtin protein, but patients with HD produce an abnormal form of it.

Currently, we have intrathecal therapies that can lower huntingtin protein, and we are beginning studies of oral therapies designed to accomplish the same goal. Over the next few years, we should learn whether these approaches can meaningfully alter disease progression.

What is most exciting is that we already know how to lower huntingtin protein. The next step is determining whether doing so changes the course of the disease. If these therapies prove successful, they could fundamentally transform how we treat HD.

Any final thoughts?

For individuals from HD families, and for clinicians caring for patients who may be at risk, this is an especially hopeful time. Decisions about genetic testing are deeply personal, and no one should feel pressured to pursue testing. At the same time, there are now numerous clinical trials evaluating huntingtin-lowering therapies that may not only improve symptoms but also slow disease progression.

The more individuals who know their genetic status and choose to participate in research, the faster we will be able to answer these critical questions. I truly believe we are closer than ever to understanding how to change the trajectory of HD.

Transcript edited for clarity.