Tetrabenazine

Tetrabenazine is a prescription medication used to treat hyperkinetic movement disorders, most notably chorea associated with Huntington's disease. It acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor, reducing the storage and release of monoamines such as dopamine from presynaptic neurons. The net effect is decreased dopaminergic activity in brain circuits that control movement, which lowers involuntary movements.

It is administered by mouth in a dose-titration regimen, with the total daily dose adjusted to balance symptom relief against adverse effects. Because its effects on mood can be significant, patients are monitored for depression, anxiety, or suicidality, especially during treatment initiation or when doses are changed. Tetrabenazine is primarily approved for Huntington's chorea; use for other conditions is often off-label or experimental in certain settings. In the United States, it has been marketed under the brand name Xenazine.

Pharmacology and metabolism: Tetrabenazine is metabolized in the liver to active compounds that contribute to VMAT2 inhibition. The drug is mainly processed by hepatic enzymes, including CYP2D6; inhibitors of CYP2D6 or individuals who are poor metabolizers can have higher exposure to the drug. Dose adjustments or avoidance may be necessary with CYP2D6 inhibitors or with hepatic impairment. The presence of active metabolites means that clinical effects may persist after the parent drug is cleared.

Safety and regulatory status: Common adverse effects include sedation, fatigue, sleep disturbance, depression or mood changes, and orthostatic hypotension, along with possible extrapyramidal symptoms such as parkinsonism or akathisia, nausea, and dizziness. Mood-related effects necessitate careful psychiatric monitoring. Tetrabenazine is one of several VMAT2 inhibitors used for movement disorders; newer agents like deutetrabenazine and valbenazine have been developed for related indications and may offer different tolerability profiles.