What is Tetrabenazine?
Tetrabenazine, sold under brands like Xenazine, Nitoman, and Xentra, is a prescription medication. It is classified as a vesicular monoamine transporter 2 (VMAT2) inhibitor, a class of drugs that reduce the levels of certain neurotransmitters in the brain. Specifically, it works by reversibly blocking VMAT2, a protein responsible for transporting neurotransmitters such as dopamine, serotonin, and norepinephrine into storage vesicles within nerve cells. By doing so, tetrabenazine decreases the amount of these neurotransmitters available for release, which is believed to help control abnormal movements, particularly through its effect on dopamine.
Primary Uses of Tetrabenazine
Tetrabenazine is FDA-approved for treating chorea, the involuntary movements associated with Huntington's disease. It is also commonly used off-label for other hyperkinetic movement disorders, such as tardive dyskinesia and Tourette syndrome.
Chorea Associated with Huntington's Disease
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by movement, cognitive, and psychiatric symptoms. Chorea, the involuntary, jerky movements seen in HD, is the primary symptom treated by tetrabenazine. Studies indicate that tetrabenazine can significantly reduce chorea in HD patients, improving motor function, although it does not treat the other symptoms or the underlying disease.
Tardive Dyskinesia
Tardive dyskinesia (TD) is a movement disorder marked by involuntary, repetitive movements, often in the face and mouth, typically resulting from long-term use of dopamine receptor-blocking medications. Tetrabenazine is used off-label for TD and has shown effectiveness in managing symptoms by reducing dopamine availability. Newer VMAT2 inhibitors are also available for TD, but tetrabenazine remains an option for certain cases.
Other Hyperkinetic Movement Disorders
Beyond its main uses, tetrabenazine has been utilized off-label for various other conditions involving excessive movement, including Tourette syndrome-related tics and dyskinesias in cerebral palsy. While its use in these cases is supported by clinical experience, formal studies may be less extensive.
How Tetrabenazine Works: The VMAT2 Inhibitor Mechanism
The action of tetrabenazine centers on its reversible inhibition of the VMAT2 protein. This affects how nerve cells handle monoamine neurotransmitters vital for movement and mood:
- Inhibition of VMAT2: Tetrabenazine binds to VMAT2 within nerve cells.
- Blocked Uptake: This binding prevents monoamines (dopamine, serotonin, norepinephrine) from entering storage vesicles.
- Increased Degradation: Unstored neurotransmitters in the cell are broken down more easily, leading to reduced levels.
- Reduced Synaptic Activity: Lower neurotransmitter levels result in less signaling. The decrease in dopamine is thought to be the primary factor in reducing involuntary movements like chorea.
Administration
Tetrabenazine is an oral medication that is typically administered several times daily. Administration requires careful, individualized adjustment by a healthcare professional to determine the optimal approach. The method of administration may be influenced by individual response and side effects, and genetic testing for CYP2D6 metabolism might be recommended.
Side Effects and Risks
Tetrabenazine has important risks, including a black box warning for increased risk of depression and suicidality, particularly in Huntington's disease patients. Patients should be closely monitored for mood changes.
Common Side Effects:
- Drowsiness/sedation
- Fatigue
- Nausea
- Insomnia
- Anxiety/agitation
- Depressed mood
Serious Side Effects:
- Neuroleptic Malignant Syndrome (NMS): A rare but severe reaction.
- QT Prolongation: Risk of abnormal heart rhythm.
- Parkinsonism: Symptoms similar to Parkinson's disease due to dopamine reduction.
- Akathisia: Severe restlessness.
Tetrabenazine vs. Newer VMAT2 Inhibitors
Newer VMAT2 inhibitors, such as deutetrabenazine (Austedo) and valbenazine (Ingrezza), have been developed since tetrabenazine's introduction. While their mechanism is similar, there are notable differences:
| Feature | Tetrabenazine (Xenazine) | Deutetrabenazine (Austedo) | Valbenazine (Ingrezza) |
|---|---|---|---|
| Dosing Frequency | Multiple times per day. | Typically twice daily. | Once daily. |
| Active Metabolite | Effects largely from metabolites. | More stable metabolite profile. | Active metabolite contributes to effect. |
| Side Effect Profile | Associated with sedation, depression, akathisia. | Possibly more favorable profile, less sedation/depression. | Generally well-tolerated. |
| FDA Approval | Chorea in Huntington's disease. | Chorea in Huntington's disease and tardive dyskinesia. | Tardive dyskinesia and chorea in Huntington's disease. |
Contraindications and Warnings
Tetrabenazine should not be used in patients with active depression or suicidal thoughts, liver impairment, or those taking other VMAT2 inhibitors or MAO inhibitors. Caution is advised in patients with heart rhythm issues or recent heart attack.
Conclusion
Tetrabenazine is primarily used to treat chorea in Huntington's disease and is also used off-label for other hyperkinetic movement disorders like tardive dyskinesia. Its action as a reversible VMAT2 inhibitor reduces dopamine and other monoamines in the brain, helping to control involuntary movements. Despite its effectiveness, significant risks exist, including a black box warning for depression and suicidality, necessitating close patient monitoring. The choice between tetrabenazine and newer VMAT2 inhibitors depends on a careful assessment of risks and benefits for each patient. Treatment requires strict medical supervision and careful adjustment of administration.
Visit the MedlinePlus Drug Information page for more details on tetrabenazine.
