PsychRounds: The Psychiatry Podcast VMAT2 Inhibitors: Valbenazine (Ingrezza) and Deutetrabenazine (Austedo)
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Mar 21, 2026 Discussion of tardive dyskinesia presentation and underlying dopamine changes. Explanation of how VMAT2 inhibition reduces presynaptic dopamine to improve movements. Comparison of valbenazine and deutetrabenazine pharmacokinetics, dosing, and metabolism. Review of side effect profiles, drug interactions, and safety concerns. Practical considerations for choosing between the two medications.
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How VMAT2 Inhibitors Treat Tardive Dyskinesia
- VMAT2 inhibitors reduce presynaptic vesicular packaging of monoamines to lower synaptic dopamine and treat tardive dyskinesia.
- Tardive dyskinesia likely arises from postsynaptic D2 upregulation after chronic antipsychotic blockade, making presynaptic modulation logical.
Evolution From Reserpine To Modern VMAT2 Drugs
- VMAT2 inhibitors existed historically (reserpine, tetrabenazine) and evolved into newer reversible, longer-acting drugs.
- Deutetrabenazine adds deuterium to extend half-life; valbenazine isolates a potent isomer with even longer half-life.
Pick VMAT2 Based On Half Life And Metabolism
- Choose valbenazine for once-daily dosing and fewer CYP2D6 interactions, and deutetrabenazine when tighter titration or multiple strengths are needed.
- Valbenazine half-life ~15–22 hrs (QD), deutetrabenazine ~9–10 hrs (BID) and is more CYP2D6 dependent.