Austedo: Uses, Dosage & Side Effects

What Is Austedo and What Is It Used For?

Austedo contains the active substance deutetrabenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor. VMAT2 is a protein located on the membrane of synaptic vesicles within monoaminergic neurons, responsible for packaging neurotransmitters—including dopamine, serotonin, norepinephrine, and histamine—into vesicles for subsequent release into the synaptic cleft. By inhibiting VMAT2, deutetrabenazine reduces the amount of these neurotransmitters, particularly dopamine, available for release. Since excessive or dysregulated dopaminergic signaling in the basal ganglia is a key factor underlying involuntary movement disorders, reducing dopamine transmission can significantly diminish abnormal movements.

Deutetrabenazine is a deuterated analog of tetrabenazine, an established VMAT2 inhibitor that has been used for decades to treat hyperkinetic movement disorders. The innovation behind Austedo lies in its molecular design: strategic replacement of six hydrogen atoms with deuterium (a stable, non-radioactive heavy isotope of hydrogen) at specific metabolic sites on the tetrabenazine molecule. This seemingly minor chemical modification has significant pharmacological consequences. Deuterium forms stronger bonds with carbon than hydrogen does, making the deuterium-carbon bond more resistant to cleavage by cytochrome P450 enzymes in the liver. This phenomenon, known as the deuterium kinetic isotope effect, slows the rate of oxidative metabolism, resulting in a longer plasma half-life, lower peak-to-trough fluctuations in blood levels, and the ability to achieve therapeutic concentrations with less frequent dosing.

After oral administration, deutetrabenazine is rapidly and extensively metabolized by carbonyl reductase enzymes to its primary active metabolites: alpha-dihydrotetrabenazine (α-HTBZ) and beta-dihydrotetrabenazine (β-HTBZ). These dihydro metabolites are the principal mediators of pharmacological activity, binding reversibly to VMAT2 and inhibiting the vesicular uptake of monoamines. The active metabolites are subsequently metabolized by CYP2D6 through O-demethylation, which is the primary route of elimination. This reliance on CYP2D6 has important clinical implications for dosing, as discussed in the dosage and interactions sections below.

Tardive Dyskinesia

Tardive dyskinesia (TD) is a persistent, often irreversible movement disorder caused by prolonged exposure to dopamine receptor-blocking agents, most commonly antipsychotic medications (both first-generation and second-generation) and certain antiemetic drugs such as metoclopramide. TD is characterized by involuntary, repetitive movements that most frequently affect the orofacial region—including lip smacking, tongue protrusion, chewing movements, facial grimacing, and puckering—but can also involve the trunk, extremities, and respiratory muscles. The condition affects an estimated 500,000 to 700,000 people in the United States alone, with prevalence rates of approximately 20–30% among patients receiving long-term antipsychotic therapy.

The pathophysiology of tardive dyskinesia is thought to involve dopamine receptor supersensitivity resulting from chronic blockade: prolonged dopamine receptor antagonism leads to upregulation and increased sensitivity of postsynaptic dopamine receptors in the nigrostriatal pathway, resulting in an exaggerated response to endogenous dopamine. By reducing the amount of dopamine available for release, Austedo helps to rebalance dopaminergic signaling and diminish involuntary movements without completely abolishing dopamine neurotransmission.

The efficacy of Austedo for tardive dyskinesia was established in two pivotal randomized, double-blind, placebo-controlled clinical trials:

• ARM-TD (Aim to Reduce Movements in Tardive Dyskinesia): This 12-week trial enrolled 117 adults with moderate to severe tardive dyskinesia. Patients were randomized to receive deutetrabenazine (titrated from 12 mg/day to a maximum of 48 mg/day) or placebo. The primary endpoint was the change in the Abnormal Involuntary Movement Scale (AIMS) score from baseline to week 12. Deutetrabenazine demonstrated a statistically significant reduction in AIMS score compared with placebo (treatment difference: −1.9 points; p = 0.019), with improvement evident as early as week 2.
• AIM-TD (Addressing Involuntary Movements in Tardive Dyskinesia): This 12-week trial enrolled 298 patients randomized to one of three fixed doses of deutetrabenazine (12, 24, or 36 mg/day) or placebo. The 36 mg/day group showed a statistically significant reduction in AIMS score compared with placebo (treatment difference: −1.4 points; p = 0.003), confirming the efficacy of deutetrabenazine at this dose level.

Importantly, long-term open-label extension studies have demonstrated that the benefits of Austedo for tardive dyskinesia are sustained over periods exceeding 2 years, with continued improvements in AIMS scores and patient-reported outcomes. Furthermore, unlike older treatments such as increasing antipsychotic doses to mask TD symptoms, Austedo directly addresses the underlying pathophysiology of the condition without necessitating changes to the patient's psychiatric medication regimen.

Huntington's Disease Chorea

Huntington's disease (HD) is a progressive, inherited neurodegenerative disorder caused by a trinucleotide (CAG) repeat expansion in the huntingtin gene on chromosome 4. The disease is characterized by a triad of motor dysfunction, cognitive decline, and psychiatric disturbances. Chorea—involuntary, irregular, purposeless movements that flow from one body part to another—is one of the most prominent and debilitating motor symptoms of HD, particularly in the early to middle stages of the disease. Chorea can interfere with voluntary movement, balance, speech, swallowing, and daily activities, significantly impacting quality of life.

The efficacy of Austedo for Huntington's disease chorea was established in the First-HD trial, a randomized, double-blind, placebo-controlled study of 90 patients with manifest Huntington's disease and choreiform movements. Patients receiving deutetrabenazine (titrated to effect, maximum 48 mg/day) showed a statistically significant reduction in the Total Maximal Chorea (TMC) score compared with placebo at 12 weeks (treatment difference: −2.5 points; p < 0.001). The trial also demonstrated improvements in the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) scores, indicating clinically meaningful benefit as perceived by both patients and clinicians.

Austedo was approved by the FDA in April 2017 for the treatment of chorea associated with Huntington's disease, and received an additional approval in August 2017 for tardive dyskinesia in adults. It was the first deuterated drug to receive FDA approval, representing a milestone in pharmaceutical chemistry. As of 2026, Austedo remains one of only two FDA-approved VMAT2 inhibitors for tardive dyskinesia (the other being valbenazine) and one of two approved treatments specifically for Huntington's disease chorea (alongside tetrabenazine).

What Should You Know Before Taking Austedo?

Contraindications

Austedo must not be used in several specific clinical situations. The most critical contraindication is in patients who are actively suicidal or who have untreated or inadequately treated depression. This is especially important in the Huntington's disease population, where depression and suicidality are inherent features of the disease itself, with suicide being one of the leading causes of death. Before initiating Austedo, healthcare providers must carefully assess the patient's psychiatric status and ensure that any depression is adequately treated and stable.

Austedo is also contraindicated in patients with hepatic impairment (Child-Pugh class A, B, or C). Because deutetrabenazine undergoes extensive hepatic metabolism via carbonyl reductase and CYP2D6, any degree of liver dysfunction can lead to significantly elevated plasma concentrations of the drug and its active metabolites, increasing the risk of serious adverse effects including QT prolongation, parkinsonism, and neuroleptic malignant syndrome (NMS).

Additional contraindications include:

• Monoamine oxidase inhibitors (MAOIs): Concomitant use of Austedo with MAOIs is contraindicated due to the risk of serotonin syndrome and hypertensive crisis. At least 14 days must elapse between discontinuation of an MAOI and initiation of Austedo, and vice versa.
• Tetrabenazine or valbenazine: Austedo must not be used in combination with other VMAT2 inhibitors, as this would result in additive depletion of monoamine neurotransmitters, increasing the risk of depression, suicidality, parkinsonism, and other serious adverse effects.
• Reserpine: At least 20 days must elapse after stopping reserpine before initiating Austedo, due to reserpine's long-lasting depletion of monoamines from nerve terminals.
• Known hypersensitivity: Austedo is contraindicated in patients with a known hypersensitivity to deutetrabenazine, tetrabenazine, or any inactive ingredient in the formulation.

Warnings and Precautions

Beyond the boxed warning, several additional warnings and precautions apply:

• Parkinsonism: Austedo causes a reduction in dopaminergic activity, which can lead to symptoms of parkinsonism including bradykinesia (slowness of movement), rigidity, tremor, and postural instability. These effects are dose-dependent and generally reversible with dose reduction or discontinuation. Patients should be monitored for signs of parkinsonism, particularly during dose titration.
• Neuroleptic malignant syndrome (NMS): A potentially fatal syndrome characterized by hyperthermia, muscle rigidity, altered consciousness, and autonomic instability has been reported with VMAT2 inhibitors. If NMS is suspected, Austedo should be discontinued immediately and intensive symptomatic treatment initiated.
• Akathisia, agitation, and restlessness: These symptoms may occur during treatment and should be monitored. If they develop, dose reduction or discontinuation may be necessary.
• QT prolongation: Austedo may cause a dose-dependent prolongation of the QT interval on electrocardiogram (ECG). It should be avoided in patients with congenital long QT syndrome, a history of cardiac arrhythmias, or in those taking other medications that prolong the QT interval. Baseline and periodic ECG monitoring may be appropriate in at-risk patients.
• Sedation and somnolence: Austedo can cause sedation and drowsiness. Patients should be cautioned about operating motor vehicles or heavy machinery until they know how the medication affects them.
• Falls: Somnolence, gait disturbance, and balance problems associated with Austedo may increase the risk of falls, particularly in elderly patients. Appropriate precautions should be taken.
• Dysphagia: Austedo may impair swallowing function. In patients with Huntington's disease, where swallowing difficulties are already common, this may increase the risk of aspiration pneumonia, a leading cause of death in HD. Careful monitoring of swallowing function is recommended.

Pregnancy and Breastfeeding

There are no adequate and well-controlled studies of Austedo in pregnant women. In animal reproduction studies, oral administration of deutetrabenazine to rats during organogenesis at doses up to approximately 3 times the maximum recommended human dose (MRHD) on a mg/m² basis did not result in adverse developmental effects. However, animal studies are not always predictive of human response. VMAT2 inhibition could theoretically affect fetal neurodevelopment by altering monoamine neurotransmitter levels during critical developmental windows. Austedo should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should be advised to use effective contraception during treatment.

It is not known whether deutetrabenazine or its metabolites are excreted in human breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue breastfeeding or to discontinue Austedo, taking into account the importance of the drug to the mother. Given the mechanism of action involving monoamine depletion, caution is warranted.

Children and Adolescents

The safety and effectiveness of Austedo have not been established in pediatric patients. Tardive dyskinesia in children is uncommon but can occur with antipsychotic use, and Huntington's disease has a juvenile-onset form. However, no clinical trials have been conducted in patients under 18 years of age, and Austedo is not currently recommended for use in this population. Pediatric patients with movement disorders should be referred to a specialist for individualized treatment recommendations.

CYP2D6 Metabolizer Status

Before initiating Austedo, healthcare providers should determine the patient's CYP2D6 metabolizer status through genotyping. CYP2D6 is the primary enzyme responsible for the O-demethylation of the active metabolites α-HTBZ and β-HTBZ. Approximately 5–10% of Caucasians and 1–2% of other populations are CYP2D6 poor metabolizers, meaning they have significantly reduced or absent CYP2D6 enzyme activity. In poor metabolizers, plasma concentrations of the active metabolites are substantially higher, increasing the risk of dose-dependent adverse effects. For this reason, the maximum recommended daily dose is 36 mg for CYP2D6 poor metabolizers, compared to 48 mg for extensive (normal) or intermediate metabolizers.

How Does Austedo Interact with Other Drugs?

Austedo's drug interaction profile is clinically important because of its dependence on CYP2D6 metabolism and its mechanism of action involving monoamine depletion. Understanding these interactions is essential for safe prescribing, particularly since many patients taking Austedo for tardive dyskinesia are concurrently treated with antipsychotics and other psychotropic medications.

Strong CYP2D6 Inhibitors

Strong CYP2D6 inhibitors are among the most clinically relevant interacting drugs for Austedo. When a strong CYP2D6 inhibitor is co-administered, the clearance of the active metabolites α-HTBZ and β-HTBZ is significantly reduced, resulting in approximately 3-fold higher plasma concentrations. This effectively converts any patient into a CYP2D6 poor metabolizer phenotype from a pharmacokinetic perspective. Common strong CYP2D6 inhibitors include paroxetine (an SSRI antidepressant), fluoxetine (another SSRI), bupropion (an antidepressant also used for smoking cessation), and quinidine (an antiarrhythmic agent). When patients are taking any of these medications concomitantly with Austedo, the total daily dose of Austedo must not exceed 36 mg/day.

It is important to note that if a strong CYP2D6 inhibitor is added to the regimen of a patient already stabilized on Austedo, the dose of Austedo may need to be reduced. Conversely, if a strong CYP2D6 inhibitor is discontinued, the dose of Austedo may need to be increased to maintain efficacy. These adjustments should always be made gradually under medical supervision.

Dopamine Antagonists

Many patients receiving Austedo for tardive dyskinesia are concurrently taking antipsychotic medications, which are dopamine receptor antagonists. While this combination is often necessary and clinically appropriate, it carries the risk of additive dopaminergic suppression. The combination may increase the risk of parkinsonism (bradykinesia, rigidity, tremor), akathisia, neuroleptic malignant syndrome, and excessive sedation. Healthcare providers should carefully monitor patients receiving this combination and adjust doses as needed. The decision to use Austedo in patients on antipsychotics should be made in consultation with the prescribing psychiatrist to ensure a coordinated treatment approach.

What Is the Correct Dosage of Austedo?

Dosing of Austedo requires a careful, individualized titration approach. The goal is to find the lowest dose that provides adequate control of involuntary movements while minimizing side effects. The starting dose, titration schedule, and maximum dose differ slightly between the two approved indications, but the general principles are the same.

Adults – Tardive Dyskinesia

For tardive dyskinesia, treatment begins with 6 mg taken orally twice daily (12 mg/day total). The dose may be increased by 6 mg/day at weekly intervals based on clinical response and tolerability. The recommended maximum dose is 48 mg/day (24 mg twice daily) for patients who are CYP2D6 extensive or intermediate metabolizers. For CYP2D6 poor metabolizers or patients concurrently taking a strong CYP2D6 inhibitor, the maximum dose is 36 mg/day (18 mg twice daily).

Adults – Huntington's Disease Chorea

For Huntington's disease chorea, the dosing schedule is identical to that for tardive dyskinesia. Treatment begins at 6 mg twice daily and is titrated upward in 6 mg/day increments at weekly intervals. The maximum dose is 48 mg/day for extensive/intermediate CYP2D6 metabolizers and 36 mg/day for poor metabolizers. Patients switching from tetrabenazine to Austedo may begin treatment with Austedo the day after the last dose of tetrabenazine, using the following approximate conversion: the first dose of Austedo should approximate the total daily tetrabenazine dose (e.g., tetrabenazine 12.5 mg three times daily = 37.5 mg/day, corresponding to approximately Austedo 18 mg twice daily = 36 mg/day). This conversion should be done under close medical supervision.

Elderly Patients

No specific dose adjustments are recommended for elderly patients based on age alone. However, elderly patients may be more susceptible to adverse effects including sedation, falls, parkinsonism, and QT prolongation. Therefore, dose titration should proceed cautiously in older adults, with careful monitoring for adverse effects. Many elderly patients take multiple medications, increasing the likelihood of drug interactions that may affect Austedo levels.

Missed Dose

If a dose of Austedo is missed, patients should take the next dose at the regularly scheduled time. They should not take a double dose to make up for a missed one. If treatment is interrupted for more than one week, re-titration from the starting dose may be necessary to re-establish the tolerated dose. This is because abrupt reinstatement of a previously tolerated dose after a treatment gap may produce unacceptable side effects due to loss of tolerance during the interruption period.

Overdose

There is limited clinical experience with overdose of deutetrabenazine. Based on the pharmacological profile and experience with tetrabenazine overdose, signs and symptoms of overdose may include excessive sedation, insomnia, nausea, vomiting, diarrhea, sweating, hypotension, confusion, and worsening of parkinsonian symptoms. In severe cases, respiratory depression, seizures, and cardiac arrhythmias (including QT prolongation and torsades de pointes) may occur. Treatment of overdose should be symptomatic and supportive. There is no specific antidote for deutetrabenazine. Cardiovascular monitoring (ECG, vital signs) should be initiated immediately, and general supportive measures including airway management should be employed as indicated. Given the large volume of distribution and extensive protein binding, hemodialysis is unlikely to be effective.

What Are the Side Effects of Austedo?

Like all medications, Austedo can cause side effects, although not everyone experiences them. The side effect profile reflects its mechanism of action as a monoamine-depleting agent. Most side effects are dose-dependent and can be managed through careful dose titration and monitoring. Understanding the frequency and nature of potential side effects is important for patients and caregivers to facilitate early recognition and appropriate management.

The following side effects have been reported in clinical trials and post-marketing experience. They are organized by frequency category according to established medical conventions:

In the pivotal ARM-TD trial for tardive dyskinesia, the most frequently reported adverse reactions that occurred at a higher incidence in the deutetrabenazine group compared to placebo were nasopharyngitis (4.2%), insomnia (4.2%), depression (3.4%), and akathisia (3.4%). In the First-HD trial for Huntington's disease chorea, the most common adverse reactions were somnolence (11%), diarrhea (9%), dry mouth (7%), fatigue (6%), and urinary tract infection (5%). Importantly, the incidence of depression in the First-HD trial was 7% in the deutetrabenazine group versus 2% in the placebo group, underscoring the importance of psychiatric monitoring.

Long-term open-label studies over periods of 1–3 years have shown that the side effect profile remains generally consistent with that observed in short-term trials, with no emergence of new safety signals over time. Most side effects are dose-related, and many resolve or improve with dose reduction. Patients experiencing bothersome side effects should consult their healthcare provider rather than abruptly stopping the medication.

How Should You Store Austedo?

Proper storage of Austedo is essential to maintain the medication's effectiveness and safety throughout its shelf life. The extended-release tablets should be stored at controlled room temperature, defined as 20°C to 25°C (68°F to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F). The medication should be kept in its original container with the cap tightly closed to protect it from moisture. Do not store Austedo in bathrooms or other humid environments, as moisture exposure can affect tablet integrity and drug stability.

Keep Austedo and all medications out of the reach and sight of children and pets. Do not transfer tablets to a different container unless using a pill organizer for short-term daily use. Do not use Austedo after the expiration date stated on the package. If you have expired or unused medication, consult your pharmacist about safe disposal methods. Many communities offer medication take-back programs that provide a convenient and environmentally responsible way to dispose of unwanted medications. Alternatively, the FDA recommends mixing unused medications with coffee grounds or cat litter in a sealed bag before placing in household trash, if no take-back program is available.

What Does Austedo Contain?

The active ingredient in Austedo is deutetrabenazine, a deuterated form of tetrabenazine. Chemically, it is described as (RR,SS)-1,3,4,6,7,11b-hexahydro-9,10-di(methoxy-d3)-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-one. The molecular formula incorporates six deuterium atoms in place of hydrogen at the methoxy groups, with a molecular weight of approximately 323.47 g/mol. Deutetrabenazine is a white to off-white crystalline powder that is slightly soluble in water.

The inactive ingredients in the tablet core include colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, mannitol, and microcrystalline cellulose. The tablet film coating contains hypromellose, polyethylene glycol, and various iron oxides and titanium dioxide for coloring. Each tablet strength is distinguished by a unique combination of shape, color, and debossing to help prevent dosing errors:

• 6 mg tablet: White to off-white, round, debossed with "SD" on one side and "6" on the other
• 9 mg tablet: Yellow, round, debossed with "SD" on one side and "9" on the other
• 12 mg tablet: Pink, round, debossed with "SD" on one side and "12" on the other

The available package presentations for total daily doses include 12 mg (two 6 mg tablets), 24 mg (two 12 mg tablets), 30 mg (combination of tablets), 36 mg, 42 mg, and 48 mg. The packaging is designed to simplify the twice-daily dosing regimen, with morning and evening doses clearly indicated. Each blister pack or bottle contains enough tablets for one month of treatment at the prescribed dose.