VMAT2 Inhibitors for Tardive Dyskinesia: What They Are and How They May Help

Twitching. Thrusting. Shaking. Grimacing.

The involuntary movements associated with tardive dyskinesia (TD) can be frustrating, embarrassing and downright debilitating. In some people, they’re so mild that they’re mostly unnoticeable. But for others, these movements are so severe that they can affect your ability to perform everyday activities and live life the way you want.

Could a VMAT2 inhibitor reduce your symptoms? Movement disorders neurologist Adam Margolius, MD, explains what VMAT2 inhibitors are and how these medications may be able to help.

What are VMAT2 inhibitors?

VMAT2 inhibitors are medications that can make involuntary movements from tardive dyskinesia less severe. They help calm the overactive brain signals that are thought to cause TD symptoms.

“These medications can be quite effective in lessening TD-related movements,” Dr. Margolius says. “While they don’t eliminate symptoms completely, they can significantly reduce movements and improve your quality of life.”

But let’s back up. To understand how VMAT2 inhibitors can help, it’s important to understand the basics of TD itself.

Tardive dyskinesia is a movement disorder that’s most often the result of taking medication to block dopamine (known as dopamine antagonists). Researchers think that, in some people, blocking this neurotransmitter can cause the brain’s dopamine receptors to become extra sensitive. And that can affect the brain’s movement-control circuits, leading to the involuntary movements that come with tardive dyskinesia.

But VMAT2 inhibitors reduce the amount of dopamine that gets released between your nerve cells. And that can help calm TD symptoms.

Different types of VMAT2 inhibitors

The U.S. Food and Drug Administration (FDA) has approved two VMAT2 inhibitors for tardive dyskinesia: deutetrabenazine (sold as Austedo® or Austedo XR®) and valbenazine (brand name Ingrezza®).

They’re similar medications that work in slightly different ways to target and block a specific cellular protein called vesicular monoamine transporter 2 (aka VMAT2).

“Both medicines work well for most people with tardive dyskinesia, so it’s often a matter of which one is more accessible and affordable for each person,” Dr. Margolius notes.

Another VMAT2 inhibitor, tetrabenazine, used to be more commonly prescribed for tardive dyskinesia. But the FDA hasn’t approved it as an official treatment for this condition, so providers are much more likely to turn to deutetrabenazine and valbenazine.

Who’s a candidate for these medications?

Not everyone with tardive dyskinesia needs to take a VMAT2 inhibitor.

“It depends on whether the movements bother you and affect your ability to participate in normal activities and everyday life,” Dr. Margolius says.

Before your provider recommends a VMAT2 inhibitor for tardive dyskinesia, they’ll want to do a few other things:

• Confirm the diagnosis. Your provider will want to be sure you’re dealing with TD before considering treatment — especially because other disorders, like Huntington’s disease, Parkinson’s disease and stroke, can look similar.
• Evaluate severity. “We don’t always have to treat TD, per se,” Dr. Margolius clarifies. “If your TD movements aren’t bothersome and aren’t really affecting your quality of life, we may just monitor them instead of treating them.”
• Address triggers. Factors like stress, anxiety or lack of sleep can sometimes make TD symptoms worse. Identifying and addressing your triggers may have a positive effect on your TD-related movements.
• Adjust other medications, if possible. Switching to a different psychiatric medication may have a positive effect on TD. But this isn’t possible for everyone, so it’s important to speak with your healthcare provider about your options — and never stop or change a psychiatric medication on your own.

VMAT2 inhibitors aren’t a good fit for everyone. Your provider may want to steer clear if you’re taking certain types of medications, or if you have or are at high risk for:

• Cardiac arrhythmia
• Parkinson’s-like symptoms
• Severe liver conditions
• Significant psychiatric concerns

How to know whether your VMAT2 inhibitor is working

When you start a VMAT2 inhibitor, your healthcare provider will want to monitor you on an ongoing basis to see how well it’s working. This will help them decide whether to adjust your dosage or change your treatment.

They’ll use a 12-item assessment called the Abnormal Involuntary Movement Scale (AIMS) to evaluate the severity of tardive dyskinesia-related movements in your face, torso, arms and legs. But that’s not the only thing they consider.

“We’re also interested in your own perception of how the medicine is working for you,” Dr. Margolius says. “If you feel that it’s helping you and has improved your quality of life, that matters just as much as what AIMS tells us — and maybe even more.”

He adds that the opposite is true, too: If your TD movements look about the same as they did before but you say you feel worse, that’s also an important factor for your provider to consider.

Final thoughts

VMAT2 inhibitors won’t cure tardive dyskinesia, but they can go a long way toward helping reduce the severity of symptoms. And Dr. Margolius says that sometimes the biggest barrier to starting these medications is simply knowing they exist.

“These treatments are relatively new within the last decade, so not everyone is aware of them,” he notes. “In my experience, a lot of people with this condition don’t even realize that treatment is available. But we definitely have options.”