VMAT2 Inhibitors for Tardive Dyskinesia: Everything You Need to Know
VMAT2 inhibitors are medications that treat movement disorders. The FDA has approved two VMAT2 inhibitors for treating tardive dyskinesia (TD) symptoms. These medications may be a good option for you if you have TD that’s affecting your quality of life.
Because TD mainly happens as a side effect of certain medications – usually antipsychotic medications – doctors often recommend tapering or changing the medication or dose to the lowest effective dose to resolve TD.
Sometimes weaning off or decreasing the medication doesn’t reduce TD symptoms. Sometimes coming off antipsychotic medications causes or worsens TD. And for some people, treating their underlying disorder is important enough that going off their medication for it isn’t an option.
If you’re on a first-generation antipsychotic medication (chlorpromazine, fluphenazine, haloperidol, perphenazine, prochlorperazine, thioridazine, or trifluoperazine) your doctor may suggest switching to a newer, second-generation option to see if this reduces your TD symptoms. These options have a lower risk of causing TD.
VMAT2 inhibitors are an option for persistent TD when changes in medications or dose aren’t sufficient.
Which VMAT2 Inhibitors Are Used for Tardive Dyskinesia?
In 2017, the FDA approved two VMAT2 inhibitors for TD, deutetrabenazine (Austedo) and valbenazine (Ingrezza). Researchers developed these two drugs in an attempt to find a treatment that could work as well on TD as an older VMAT2 inhibitor, tetrabenazine (Xenazine) while reducing the number of side effects.
Both Austedo and Ingrezza turned out to be safer drugs with the same effectiveness on symptoms.
Doctors used to prescribe tetrabenazine off-label for TD, but it is FDA approved only for the treatment of the abnormal movements seen in Huntington’s disease and causes more serious side effects.
Deutetrabenazine (Austedo, Austedo XR) reduces involuntary movements caused by TD. The FDA also approved it for treating involuntary movements or chorea seen in Huntington’s disease. The extended-release tablet can be taken once a day, or your doctor may prescribe a twice-a-day tablet.
Valbenazine (Ingrezza) helps reduce the involuntary movements that result from TD. It's also approved for treating involuntary movements or chorea seen in Huntington’s disease. You take it in capsule form once a day or you can sprinkle it on soft foods once a day.
How Do VMAT2 Inhibitors Work?
VMAT2 stands for vesicular monoamine transporter type 2. VMAT2 is a protein that is responsible for taking dopamine molecules inside brain cells and putting them into a protective package called a vesicle. The vesicle helps dopamine travel safely through the gap between one nerve cell and another. Without the vesicle packaging, dopamine breaks down before it gets to the next cell.
One of the roles dopamine plays in your body is to regulate movement. Typically, VMAT regulates how much dopamine goes from cell to cell. VMAT2 inhibitors are dopamine-depleting drugs. They stop VMAT proteins from putting dopamine into vesicles and reduce the amount of dopamine action from cell to cell.
How Effective Are VMAT2 Inhibitors?
In order to test how well VMAT2 inhibitors work on TD, researchers conducted several clinical trials for each drug. These trials resulted in a significant improvement in symptoms for many people in the studies.
In one study, 97% of people who took VMAT2 inhibitors had improved TD, with 25% experiencing "significant improvement" and 41% experiencing "much improvement" in their involuntary movements.
They also reported a better quality of life overall. Many were able to go to work and school again and participate in activities they couldn’t before.
Are VMAT2 Inhibitors Safe?
Studies have shown the FDA-approved VMAT2 inhibitors to be safe treatments for TD. Like any medication, they can cause side effects, and some can be serious.
Rarely, valbenazine (Ingrezza) may have serious side effects such as:
- Dizziness
- Muscle aches
- Increases in weight or blood sugar
- Abnormal muscle movements
- Irregular heart rhythm
- Rash
- Swelling of the face, lips, and mouth
Also rarely, deutetrabenazine (Austedo) can cause:
- Slight shaking
- Stiffness
- Trouble moving
- Anxiety
- Depression
- Agitation
- Restlessness
- Constipation
- Urinary tract infection
- Irregular heart rhythm
Austedo, Austedo XR, and Ingrezza come with a black box warning from the FDA. A black box warning is the most serious warning the FDA gives to alert you about drug effects that may be dangerous.
The warning notes the risk of depression and suicidal thoughts in patients with Huntington’s disease (not TD). Talk to your doctor if you have a history of depression or thoughts of suicide.
What Are the Common Side Effects of VMAT2 Inhibitors?
Like most drugs, VMAT2 can cause some side effects when you take them. The most common side effects are not severe but may cause discomfort or disrupt your daily life.
Common valbenazine (Ingrezza) side effects include:
- Sleepiness
- Tiredness
- Hives
- Rash
- Trouble staying or getting to sleep
Common deutetrabenazine (Austedo) side effects include:
- Headache
- Diarrhea
- Tiredness
- Sleepiness
- Dry mouth
How Much Do VMAT2 Inhibitors Cost?
Costs for drugs depend on several factors, including the pharmacy you visit and the health care coverage you have.
Valbenazine (Ingrezza) ranges in cost around $300 per pill, depending on dosage. This comes out to more than $100,000 per year.
Deutetrabenazine (Austedo) has an out-of-pocket cost of between $5,000 and $8,000 for 60 tablets. Austedo XR has an out-of-pocket cost of between $2,500-$15,500 for 30 tablets.
These costs are based on out-of-pocket cash prices. Most people do not have to pay this full amount, especially with insurance. Costs on Medicare are much lower.
Many drug manufacturers offer programs that will reduce out-of-pocket costs for prescriptions. These programs are free but may have some rules or restrictions.
Ingrezza offers a one-month free trial for people new to the drug through the Ingrezza Start program. People with commercial insurance may qualify for a $0 monthly copay with an Ingrezza savings card from the INBRACE Assistance Program.
Austedo is available through the Teva Cares Foundation, a patient assistance program that offers cost-free or discounted medicines, as well as copay programs, to people with low income or those who are uninsured/under-insured and meet specific criteria. People with commercial insurance may qualify for a $0 monthly copay from the Teva Shared Solutions patient support program.
Who Should Not Take VMAT2 Inhibitors?
You shouldn’t take more than one type of VMAT2 inhibitor at a time. If you’re pregnant or thinking of getting pregnant, talk to your doctor. There aren’t many studies on VMAT2 inhibitors and pregnancy. In animal studies, they increased stillbirths and other serious issues.
Certain medications can affect your VMAT2 inhibitors or cause more serious side effects if you take VMAT2 inhibitors.
If you take deutetrabenazine, take caution if you also take antipsychotics, tricyclic antidepressants, certain heart medications, and antibiotics, which can increase your risk of irregular heart rate.
If you take valbenazine, take caution if you also take certain seizure or heart medications, antibiotics, and herbal supplements.
Is a VMAT2 Inhibitor Right for Me?
VMAT2 inhibitors are effective and safe for treating TD, but only you and your doctor can decide if they are right for you. Everyone responds to treatment differently.
As you decide whether to stop the treatment causing your TD or try TD treatment medication, you can ask yourself:
- How does TD affect you and your day-to-day life?
- How does your medication help you and your day-to-day life?
- Do you experience other unwanted side effects from your medication, as well as TD?
- How likely are you to relapse if you come off your medication entirely?
While studies show VMAT2 inhibitors to be the most effective treatment for TD, there are other medication options that doctors may prescribe off-label. These include:
- Amantadine (Gocovri, Symmetrel), a Parkinson’s disease drug
- Baclofen (Gablofen, Lioresal), a muscle relaxant
- Botulinum toxin (Botox), an injection of muscle relaxant
- Clonazepam (Klonopin), a GAGA agonist/benzodiazepine
- Clozapine (Clozaril), an atypical antipsychotic
- Gabapentin (Neurontin), an anticonvulsant
- Levetiracetam (Keppra), an antiepileptic drug
- Piracetam, a drug to treat myoclonus
- Propanolol (Inderal), a beta-blocker
- Zolpidem (Ambien), a sleep medication
People with severe TD symptoms who haven’t responded to other treatments may benefit from deep brain stimulation. A surgeon implants a pacemaker-like device that sends electrical impulses to specific areas of the brain to help lessen symptoms.
Things to Consider When Choosing a VMAT2 Inhibitor
The following key points about VMAT2 inhibitors can help you decide if they’re right for treating your tardive dyskinesia.
VMAT2 Inhibitors are an option for persistent TD. Changing medications or tapering the dose may ease TD. That’s not always an option and sometimes stopping or switching the medication doesn’t make a difference. VMAT2 inhibitors are treatment options for people living with TD.
They’re safe and effective. Deutetrabenazine (Austedo, Austedo XR) and valbenazine (Ingrezza) are VMAT2 inhibitors the FDA has approved for treating TD. The majority of people who take them see a difference in their TD symptoms. The side effects are typically mild.
They can be expensive, but there are ways to reduce cost. The out-of-pocket costs for both FDA-approved VMAT2 inhibitor options are in the thousands, but it’s unlikely you’ll pay that much. Manufacturers offer programs and coupons that reduce cost, and there are organizations that help with financial assistance for TD treatments.
Certain groups shouldn’t take them. If you’re pregnant or considering pregnancy, your doctor may caution against VMAT2 inhibitors. If you take certain medications, such as antibiotics, and certain heart medications, VMAT2 inhibitors may interact with them, or vice versa.