This guide provides essential information about Austedo® (deutetrabenazine) and its approved medical uses. Designed as an educational resource, it offers insights into how this prescription medication works in the body to manage specific movement disorders. Readers will learn about the two primary conditions Austedo is indicated to treat: chorea associated with Huntington's disease and tardive dyskinesia. The article also covers important safety considerations, including the boxed warning regarding depression and suicidality in patients with Huntington's disease. This factual overview is intended to help patients and caregivers understand the medication's purpose and have more informed discussions with their healthcare providers.
When facing a diagnosis involving involuntary movements, understanding the treatment options available is a critical step in the healthcare journey. Austedo® (deutetrabenazine) is a prescription medication that has been approved for use in adults to manage specific movement disorders. This guide provides comprehensive, factual information about Austedo medication uses, offering insights into how it works, which conditions it treats, and what patients should know before starting therapy. The information presented here is for educational purposes and is derived from official prescribing information and reputable medical sources.
Austedo (deutetrabenazine) is a prescription drug that belongs to a class of medications known as vesicular monoamine transporter 2 (VMAT2) inhibitors . It was first approved by the U.S. Food and Drug Administration (FDA) in 2017, marking a significant milestone in pharmaceutical development as the first deuterated drug to receive approval . Deuteration is a process where specific hydrogen atoms in the drug molecule are replaced with deuterium, a stable isotope of hydrogen, which affects how the body metabolizes the medication .
The medication is available in two formulations: Austedo tablets (immediate-release) and Austedo XR® extended-release tablets . Both formulations contain the same active ingredient, deutetrabenazine, but they are designed to be taken on different schedules, which will be discussed later in this guide.
According to the official prescribing information, Austedo is indicated in adults for the treatment of two specific conditions: chorea associated with Huntington's disease and tardive dyskinesia .
Huntington's disease is a progressive, hereditary neurodegenerative disorder that affects movement, cognition, and behavior. One of the most visible symptoms of Huntington's disease is chorea—involuntary, irregular, jerking movements that can affect the face, trunk, and limbs . These movements are caused by dysfunctional dopamine signaling in the brain.
Austedo works by inhibiting VMAT2, which reduces the uptake of dopamine into synaptic vesicles, leading to decreased dopamine release from nerve terminals . This reduction in dopaminergic activity helps control the involuntary movements associated with chorea. The FDA granted Austedo orphan drug designation for the treatment of Huntington's disease, reflecting its importance in addressing this rare condition .
Tardive dyskinesia (TD) is a condition characterized by repetitive, involuntary movements, typically involving the face, mouth, tongue, and sometimes the limbs and trunk . TD most commonly develops as a side effect of long-term treatment with antipsychotic medications or other drugs that block dopamine receptors .
The condition can be stigmatizing and significantly impact quality of life. While second- and third-generation antipsychotics have lower annual incidence rates of TD compared to first-generation agents (3.9% versus 5.5%), the risk remains substantial, especially as antipsychotics are increasingly used to treat a wider range of conditions including mood disorders and autism spectrum disorders .
The European Medicines Agency (EMA) specifically notes that Austedo is indicated for moderate to severe tardive dyskinesia in adults . Clinical studies have demonstrated that Austedo is more effective than placebo in reducing the severity of involuntary movements as measured by the Abnormal Involuntary Movement Scale (AIMS) .
Understanding how Austedo works provides valuable insight into its therapeutic uses. As mentioned, Austedo is a VMAT2 inhibitor. VMAT2 is a protein responsible for packaging neurotransmitters—including dopamine, serotonin, norepinephrine, and histamine—into vesicles for storage and release .
Austedo itself is a prodrug, meaning it is rapidly converted in the body to its active metabolites, primarily α-dihydrotetrabenazine (α-HTBZ) and β-dihydrotetrabenazine (β-HTBZ) . These active metabolites reversibly inhibit VMAT2 with high potency (IC50 of approximately 4.5 nM) .
By inhibiting VMAT2, the medication prevents dopamine from being packaged into vesicles. Unprotected dopamine in the nerve terminal is then broken down by enzymes, leading to reduced dopamine release when neurons fire . This reduction in dopaminergic signaling is believed to be the mechanism by which Austedo controls the involuntary movements characteristic of both Huntington's chorea and tardive dyskinesia .
A key innovation of Austedo is its deuterated structure. The replacement of specific hydrogen atoms with deuterium creates stronger carbon-deuterium bonds, which slows the rate of metabolism by the CYP2D6 enzyme system . This results in a longer half-life of active metabolites (approximately 9-10 hours compared to 5-7 hours for non-deuterated tetrabenazine) and more stable plasma concentrations . These pharmacokinetic advantages allow for less frequent dosing and may contribute to improved tolerability.
The dose of Austedo is individualized for each patient based on reduction of symptoms and tolerability . Here are key dosing insights from the prescribing information:
For patients not switching from tetrabenazine:
Huntington's disease chorea: The recommended starting dose is 6 mg administered orally once daily .
Tardive dyskinesia: The recommended starting dose is 12 mg per day (6 mg twice daily) .
For both conditions, the dose may be increased at weekly intervals in increments of 6 mg per day up to a maximum recommended daily dosage of 48 mg .
Important administration instructions:
Austedo tablets should be taken with food and total daily dosages of 12 mg or above should be given in two divided doses .
Austedo XR extended-release tablets can be taken with or without food and are administered once daily .
Tablets should be swallowed whole and not chewed, crushed, or broken .
For patients switching from tetrabenazine (the related VMAT2 inhibitor), specific conversion tables are provided in the prescribing information to guide the initial dosing regimen .
Austedo carries several important warnings that patients and caregivers should understand. This information is not intended to alarm but to empower patients to have informed discussions with their healthcare providers.
Austedo has a boxed warning—the most serious warning from the FDA—regarding the increased risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntington's disease . This warning exists because patients with Huntington's disease are already at increased risk for depression and suicidality, and Austedo may further increase this risk .
Before prescribing Austedo, healthcare providers must balance the risks of depression and suicidality with the clinical need for treatment of chorea . Patients receiving Austedo should be closely monitored for the emergence or worsening of depression, suicidality, or unusual changes in behavior . Austedo is contraindicated in patients who are suicidal or have untreated or inadequately treated depression .
Clinical Worsening in Huntington's Disease: Huntington's disease is progressive, and VMAT2 inhibitors may cause worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for Austedo .
QT Prolongation: Austedo may prolong the QT interval, though the degree is not clinically significant within the recommended dosage range. It should be avoided in patients with congenital long QT syndrome or a history of cardiac arrhythmias .
Neuroleptic Malignant Syndrome (NMS) : Though not observed with Austedo, NMS has been reported with the related drug tetrabenazine. NMS is a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability .
Akathisia, Agitation, and Restlessness: Austedo may increase the risk of these symptoms in patients with Huntington's disease and tardive dyskinesia .
Parkinsonism: Parkinson-like symptoms including bradykinesia, rigidity, and tremor have been reported .
Sedation and Somnolence: Sleepiness is one of the most common side effects, affecting more than 1 in 10 patients . This may impair the ability to drive or operate machinery .
For patients with Huntington's disease, the most common adverse reactions (>8% and greater than placebo) include somnolence, diarrhea, dry mouth, and fatigue . For patients with tardive dyskinesia, the most common adverse reactions (occurring in ≥4% of patients and greater than placebo) include nasopharyngitis (common cold) and insomnia .
Austedo is contraindicated in several situations :
Patients with Huntington's disease who are suicidal or have untreated/inadequately treated depression
Patients with hepatic impairment
Patients taking reserpine (at least 20 days should elapse after stopping reserpine before starting Austedo)
Patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy
Patients taking tetrabenazine or valbenazine (Ingrezza®)
Several important drug interactions should be discussed with healthcare providers:
Strong CYP2D6 Inhibitors: Drugs like quinidine, paroxetine, fluoxetine, and bupropion can increase exposure to Austedo's active metabolites. The maximum recommended dose in patients taking these medications is 36 mg per day .
Alcohol or Other Sedating Drugs: May have additive sedation and somnolence effects .
Antipsychotics and Other Dopamine Antagonists: Caution is warranted due to potential additive effects.
Austedo is one of two VMAT2 inhibitors commonly prescribed for these conditions, the other being Ingrezza® (valbenazine) . Both medications are effective for treating tardive dyskinesia and chorea associated with Huntington's disease, and both are included in the American Psychiatric Association's treatment guidelines for tardive dyskinesia .
Key differences include:
Austedo is available in both twice-daily (immediate-release) and once-daily (extended-release) formulations, while Ingrezza is taken once daily .
Neither medication is currently available as a generic, though a generic version of valbenazine has been approved but is not yet available .
Both carry boxed warnings regarding depression and suicidality in Huntington's disease patients .
Direct comparative studies between Austedo and Ingrezza have not been conducted, so it is not clear whether one is superior to the other for treating these conditions . The choice between them depends on individual patient factors, other medications, and healthcare provider judgment.
Approximately 7-10% of the population are "poor metabolizers" due to genetic variations in the CYP2D6 enzyme . These individuals have little to no CYP2D6 activity and are likely to have 3- to 4-fold increased exposure to active metabolites following standard doses . For these patients, the total daily dosage of Austedo should not exceed 36 mg .
Austedo is contraindicated in patients with hepatic impairment due to increased drug exposure and risk of adverse effects .
Based on animal data, Austedo may cause fetal harm, and patients should discuss pregnancy planning with their healthcare providers .
Austedo (deutetrabenazine) represents an important treatment option for adults living with chorea associated with Huntington's disease or tardive dyskinesia. As a VMAT2 inhibitor, it works by modulating dopamine signaling in the brain to reduce involuntary movements. Its innovative deuterated structure offers pharmacokinetic advantages that may contribute to improved tolerability and convenient dosing schedules.
This guide provides educational information about Austedo medication uses, but it is not a substitute for professional medical advice. Patients should have thorough discussions with their healthcare providers about whether Austedo is appropriate for their specific situation, considering their full medical history, other medications, and individual risk factors. If Austedo is prescribed, close monitoring by the healthcare team and open communication about any concerning symptoms are essential components of safe and effective treatment.