What is a VMAT2 Inhibitor?
Ingrezza, with the generic name valbenazine, belongs to a class of medications called vesicular monoamine transporter 2 (VMAT2) inhibitors. This class of drugs works differently from other psychiatric medications, such as antipsychotics, which block dopamine receptors directly. Instead, Ingrezza and other VMAT2 inhibitors act on a specific protein called VMAT2 to regulate neurotransmitter levels indirectly.
VMAT2 is a transporter protein located on the membranes of synaptic vesicles inside neurons, particularly in the nigrostriatal and mesolimbic regions of the brain. Its role is to package monoamine neurotransmitters, such as dopamine, serotonin, and norepinephrine, from the cell's cytoplasm into these vesicles for storage and later release into the synaptic cleft. By reversibly inhibiting VMAT2, Ingrezza effectively reduces the amount of dopamine packaged into these vesicles. As a result, less dopamine is released when the neuron is activated, which is believed to reduce the excessive dopamine signaling linked to involuntary movements.
Approved Uses for Ingrezza
Ingrezza is FDA-approved for the treatment of two specific movement disorders in adults.
Tardive Dyskinesia (TD)
TD is a neurological disorder characterized by repetitive, involuntary muscle movements, most commonly affecting the face, lips, tongue, and jaw. It is often a side effect of long-term use of antipsychotic medications or certain stomach medications. Ingrezza was the first drug approved specifically for the treatment of TD, providing a targeted approach to managing these uncontrollable movements. Clinical trials showed that Ingrezza significantly reduced TD symptoms compared to placebo, with benefits seen within weeks of starting treatment.
Chorea Associated with Huntington's Disease (HD)
In addition to TD, Ingrezza is also approved for treating chorea in adults with Huntington's disease. Chorea is a hallmark symptom of HD, a genetic disorder, and involves involuntary, jerky, and random movements that can affect the limbs, trunk, and face. While Ingrezza can help manage these uncontrollable movements, it does not treat other symptoms of Huntington's disease, such as cognitive or emotional issues. The FDA approval for this indication came in 2023, based on clinical trial data demonstrating a significant reduction in chorea severity scores.
How to Take and What to Expect with Ingrezza
Ingrezza is typically taken once daily, with or without food. It is available in capsule form and a sprinkle capsule formulation for patients who have difficulty swallowing. While some improvements may be noticeable within a couple of weeks, the full therapeutic effect can take longer to develop, sometimes months. It is important to continue treatment as directed by a healthcare provider and not to stop abruptly.
Ingrezza vs. Austedo: A Comparison
Both Ingrezza (valbenazine) and Austedo (deutetrabenazine) are VMAT2 inhibitors used to treat TD and HD chorea. However, they have distinct differences.
| Feature | Ingrezza (valbenazine) | Austedo (deutetrabenazine) |
|---|---|---|
| Drug Class | Selective VMAT2 Inhibitor | VMAT2 Inhibitor |
| Mechanism | Selectively inhibits VMAT2 to reduce dopamine release. | Inhibits VMAT2 and also affects other neurotransmitters (serotonin, norepinephrine). |
| Dosing Frequency | Once daily. | Twice daily. |
| FDA-Approved Uses | Tardive Dyskinesia, HD chorea. | Tardive Dyskinesia, HD chorea. |
| Formulations | Capsules, sprinkle capsules. | Oral tablet. |
| Half-Life | 15–22 hours. | Around 10 hours. |
| Primary TD Use | Can be added to existing stable mental health regimens. | May interact with other medications. |
| Side Effect Profile | May have a lower risk of depression than Austedo in some cases. | Higher risk of depression and suicidal ideation in HD patients than Ingrezza. |
Important Safety Information and Side Effects
Like all medications, Ingrezza carries a risk of side effects, some of which can be serious. It is crucial for patients and caregivers to be aware of these potential risks.
Boxed Warning
For patients taking Ingrezza for Huntington's disease chorea, there is a boxed warning regarding the increased risk of depression and suicidal thoughts or behavior. Symptoms of depression are common in HD, and VMAT2 inhibitors can worsen them. Close monitoring is essential for these patients.
Common Side Effects
- Somnolence/Sedation: Feeling sleepy or drowsy is the most common side effect.
- Fatigue: A general feeling of tiredness is also frequently reported.
- Rash or Hives: Skin reactions like raised, itchy areas can occur.
- Insomnia: Some patients experience trouble sleeping.
- Balance Problems: Dizziness, difficulty with coordination, and falls may happen.
Serious Side Effects
- Neuroleptic Malignant Syndrome (NMS): This is a rare but potentially fatal reaction, characterized by high fever, stiff muscles, confusion, and changes in heart rate or blood pressure.
- Parkinsonism: Symptoms resembling Parkinson's disease, such as shaking, stiffness, and difficulty moving, may occur. The dose may need to be reduced or discontinued if this happens.
- QT Prolongation: Ingrezza can affect heart rhythm, potentially causing a rare, dangerous condition called QT prolongation. It should be avoided in patients with congenital long QT syndrome or other specific heart rhythm problems.
- Hypersensitivity Reactions: Severe allergic reactions, including angioedema (swelling of the face, lips, tongue) can occur and may be fatal.
Conclusion
In summary, Ingrezza (valbenazine) is a selective VMAT2 inhibitor, a distinct class of medication designed to regulate dopamine signaling in the brain. Unlike traditional antipsychotics, it works by inhibiting the VMAT2 protein, which reduces the release of dopamine into neural synapses. This targeted action makes Ingrezza an effective treatment for the involuntary movements associated with tardive dyskinesia and Huntington's disease chorea. While generally well-tolerated, its safety profile includes important warnings, particularly regarding depression and suicidality in Huntington's patients, and requires careful monitoring. Patients should always follow their healthcare provider's guidance and be aware of the differences between Ingrezza and other VMAT2 inhibitors like Austedo. For more information on the medication, one can consult the full prescribing information from the FDA.
