Deutetrabenazine

Deutetrabenazine is a deuterated vesicular monoamine transporter type 2 (VMAT2) inhibitor used to treat movement disorders characterized by involuntary movements. It is a deuterated analog of tetrabenazine and is marketed under the brand name Austedo in many countries. By inhibiting VMAT2, deutetrabenazine reduces the vesicular storage and release of monoamines, particularly dopamine, which helps lessen hyperkinetic movements.

Indications include chorea associated with Huntington’s disease and tardive dyskinesia resulting from long-term antipsychotic therapy. The medication is taken orally and is usually started at a low dose with gradual titration based on clinical response and tolerability. Dosing is individualized and often taken with meals to improve absorption.

Pharmacokinetics and metabolism are hepatic, with active metabolites contributing to the clinical effect. The deuterated structure is designed to modify the drug’s pharmacokinetic profile, potentially producing a more stable exposure and different tolerability compared with nondeuterated tetrabenazine. The drug is metabolized by liver enzymes, including cytochrome P450 pathways, and drug interactions with strong CYP inhibitors or inducers may require dose adjustments.

Common adverse effects reported with deutetrabenazine include sleep disturbance, fatigue, nausea, diarrhea, and restlessness. Mood changes, including depression and suicidality, can occur, and there is a potential for extrapyramidal symptoms. Serious concerns include rare cases of QT interval prolongation and effects on mood or mental state; caution is advised in patients with a history of depression or suicide risk. Use with monoamine oxidase inhibitors or other VMAT2 inhibitors is generally avoided or carefully managed.

Overall, deutetrabenazine provides a targeted option for reducing involuntary movements in specific movement disorders, with dosing tailored to balance efficacy and tolerability.