Tetrabenazine (Xenazine)

What it treats

Tetrabenazine is approved by the U.S. Food and Drug Administration for chorea associated with Huntington disease.

It's also been used off-label for tardive dyskinesia and for other hyperkinetic movement disorders (tics in Tourette syndrome, some dystonias). For TD, most prescribers now reach for deutetrabenazine or valbenazine first because they're easier to dose and better tolerated. Tetrabenazine still has a role when the newer drugs aren't accessible or when a patient has responded to it in the past.

How it works

Tetrabenazine blocks a small protein called VMAT2 (vesicular monoamine transporter 2) inside monoamine nerve cells. VMAT2 is what loads dopamine into the storage packets that get released at the nerve terminal. Block the loading step, less dopamine gets released.

In Huntington chorea and tardive dyskinesia, less dopamine release in motor circuits means quieter involuntary movements. The mechanism is presynaptic, which is different from how antipsychotics work.

Receptor mechanism (detail)

Tetrabenazine inhibits the vesicular monoamine transporter type 2 (VMAT2), depleting presynaptic dopamine (and to a smaller degree serotonin and norepinephrine) available for release. Its active metabolites are cleared largely by CYP2D6, which is why a patient's CYP2D6 status matters at higher doses.

Potency and typical dosing pattern

Ranges are typical framework only, not a prescription for any individual.

Starting dose is 12.5 mg once in the morning. The dose is titrated weekly by 12.5 mg per day. Once the daily dose exceeds 37.5 mg, it's split into three-times-daily dosing. The usual therapeutic range for Huntington chorea runs from 37.5 to 100 mg per day.

CYP2D6 genotyping is recommended before doses go above 50 mg per day. In extensive metabolizers, the maximum daily dose is 100 mg (up to 37.5 mg per single dose). In poor metabolizers, the maximum is 50 mg per day (up to 25 mg per single dose). Combining with a strong CYP2D6 inhibitor triggers the same lower ceiling.

Safety monitoring

• Depression and suicidal thoughts. This is the piece that most shapes clinical decisions with tetrabenazine.
• QTc on ECG in patients with cardiovascular risk factors or on other QT-prolonging medications.
• Parkinsonism, akathisia, and sedation. Dopamine-depletion side effects can look like the movement disorder returning.
• CYP2D6 genotype if the dose is going above 50 mg per day.
• Blood pressure and heart rate during titration.

What to expect

Some reduction in movements often shows up in the first two to four weeks of titration. Because tetrabenazine has a short half-life and is dosed three times daily, the effect fluctuates through the day, and patients sometimes notice that some hours are quieter than others.

Early side effects are usually sedation, a slightly slowed feeling, and sometimes low mood. Splitting the dose more evenly and slowing the titration can help.

Common side effects

The commonly reported ones include:

• Sedation or somnolence.
• Depression or low mood.
• Insomnia (paradoxically, some patients).
• Fatigue.
• Nausea.
• Akathisia (a restless feeling).
• Parkinsonism (slowness, stiffness).
• Balance disturbance.

Many settle as the dose stabilizes. If a side effect is dose-related, a small pull-back often solves it.

Serious side effects and warnings

Serious problems are uncommon, but a few need to be understood before starting.

Boxed warning. Tetrabenazine can increase the risk of depression and suicidal thoughts or actions in patients with Huntington disease. Anyone with Huntington disease taking it should be watched closely for mood change, and it's generally avoided in people with active, untreated depression, recent suicidal thinking, or a history of suicide attempts. The boxed warning names the Huntington population, but the mechanism applies broadly and mood should be tracked in any patient.

• QT prolongation. Higher doses can lengthen QTc. Combining with other QT-prolonging drugs (some antipsychotics, methadone, certain antibiotics) needs care.
• Neuroleptic malignant syndrome. Rare but reported. Fever, rigidity, altered mental status, autonomic instability. Emergency.
• Parkinsonism and akathisia. Dose reduction usually helps.
• Sedation and impaired driving, particularly during titration.

Sexual and relational effects

Sexual side effects aren't a headline feature, but reduced desire, delayed orgasm, or erectile changes can happen, often tied to sedation, depression, or dopamine depletion. If sexual function shifts after starting it, that's worth raising with the prescriber.

Weight, appetite, and sleep

Weight and appetite aren't strongly affected. Sleep tilts sedating for most, and some patients notice insomnia. Adjusting the timing of the last daily dose can help.

Starting and dosing basics

This section is general background, not a dosing instruction for any individual. The right dose is a decision for a prescriber.

Tetrabenazine comes as 12.5 mg and 25 mg tablets, scored so they can be split. Once the daily dose is above 37.5 mg, dosing is split three times a day. Because of the short half-life, missing a dose is felt more quickly than with the newer VMAT2 inhibitors.

Missed doses and interactions

If you miss a dose, take it as soon as you remember unless the next scheduled dose is close. Don't double up.

The main interactions:

• Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) raise blood levels; the max dose drops.
• MAO inhibitors shouldn't be combined.
• Reserpine and tetrabenazine together is a hard no.
• Other VMAT2 inhibitors (deutetrabenazine, valbenazine) shouldn't be combined.
• QT-prolonging drugs need caution.
• Alcohol adds to sedation and depression risk.

Give every prescriber and pharmacist a full list of your medications and supplements.

Stopping and tapering

Tetrabenazine can generally be stopped without a formal taper. Chorea will typically return over days once the drug is out; the short half-life is what makes that return feel abrupt. If a break is planned, the return of movements should be expected and worked through with the prescriber ahead of time.

Pregnancy and breastfeeding

Data in pregnancy is limited. Use is generally reserved for cases where the movement disorder is functionally significant. Whether the drug or its active metabolites pass into breast milk in meaningful amounts isn't well characterized. Anyone who is pregnant, planning a pregnancy, or breastfeeding should talk it through with their prescriber so specific risks and benefits can be weighed.

Cost and generic availability

Tetrabenazine has been available as a generic for several years and is much less expensive than the newer VMAT2 inhibitors. The brand (Xenazine) is still made. Generic tetrabenazine contains the same active medication and works the same way.

Common questions

Why not just use this instead of deutetrabenazine or valbenazine? Cost is the main reason someone might. Otherwise, the newer VMAT2 inhibitors are usually preferred: fewer daily doses, smoother plasma levels, less depression signal, and generally easier tolerability. Tetrabenazine still works, and some patients do very well on it.

Do I have to get genotyped? Only if the daily dose is going above 50 mg per day. Below that, most patients can be started without a CYP2D6 test.

Will my chorea come back if I stop? Yes, over days. Tetrabenazine treats the movements; it doesn't change the underlying disease.

Is this an antipsychotic? No. It works on the presynaptic side (blocking dopamine loading), not by blocking receptors the way antipsychotics do. That said, dose-related side effects can look similar (parkinsonism, akathisia, sedation).

Questions to ask your prescriber

• What are we hoping this treats, and how will we know it's working?
• What's the plan if I develop low mood on it?
• Given my other medications, should I be genotyped before going higher?
• What signs would tell you the dose is too high?
• If it doesn't work well enough, what are the next options?

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes, and current as of June 8, 2026.

• U.S. Food and Drug Administration. Tetrabenazine (Xenazine) prescribing information.
• DailyMed, U.S. National Library of Medicine. Tetrabenazine label.
• MedlinePlus, U.S. National Library of Medicine. Tetrabenazine.
• National Institute of Mental Health. Mental health medications.
• American Academy of Neurology. Tardive syndromes treatment guideline.
• Huntington Study Group. Recommendations on the use of VMAT2 inhibitors for chorea in Huntington disease.