deutetrabenazine

General Information

Deutetrabenazine (Austedo/Austedo XR) is a VMAT2 inhibitor approved for tardive dyskinesia and chorea associated with Huntington disease. Deuterium substitution slows metabolism compared with tetrabenazine, producing steadier plasma exposure with twice-daily IR or once-daily XR dosing.

Allows clinicians to reduce hyperkinetic movements while maintaining antipsychotic therapy; randomized trials demonstrate AIMS improvements within six weeks that persist in long-term extensions.

The compare view and deutetrabenazine evidence feed can support shared decision-making and coordination of VMAT2 titration alongside antipsychotic adjustments; the schizophrenia hub includes related tardive dyskinesia resources.

Often chosen when valbenazine is ineffective, poorly tolerated, or not covered; mood monitoring is important given the boxed warning for depression and suicidality in Huntington disease.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Reversibly inhibits VMAT2, decreasing vesicular packaging of dopamine and other monoamines to dampen hyperkinetic movements.

Deuterium substitution prolongs the half-life of active metabolites compared with tetrabenazine, reducing peak-to-trough fluctuations.

• VMAT2 inhibitor; no direct dopamine receptor antagonism.

Metabolism and Pharmacokinetics

• Converted by carbonyl reductase to active α- and β-dihydrotetrabenazine metabolites.
• Metabolites are substrates of CYP2D6; elimination half-life ~9–10 hours (longer with XR formulation).
• Excreted predominantly in urine (~75%) as metabolites; hepatic impairment markedly increases exposure and is contraindicated.

Dosing and Administration

• Immediate-release (label): begins at 6 mg once daily with food; titrate by 6 mg/day at weekly intervals (as divided twice-daily doses) to a typical 12 mg twice-daily target; maximum 48 mg/day.
• Extended-release (label): begins at 12 mg once daily with food; titrate by 6 mg/day each week up to 48 mg once daily.
• Label limits total daily dose to 36 mg/day in poor CYP2D6 metabolizers or when co-administered with strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, bupropion, quinidine).
• Contraindicated in hepatic impairment. If therapy is interrupted for >1 week, label recommends restarting titration; interruptions ≤7 days may resume the prior dose.
• When converting from tetrabenazine, label dosing typically starts at roughly half the total daily tetrabenazine dose with retitration to response.

Monitoring & Labs

• Baseline and follow-up AIMS scoring (and functional impact) to document benefit and support payer renewals.
• Mood symptoms (depression, suicidality) and sleep changes during titration, even outside Huntington disease populations.
• QTc monitoring when cardiac risk exists or when QT-active drugs/CYP2D6 inhibitors are co-prescribed.
• Sedation and falls risk, especially in older adults and when other CNS depressants are used.

Deutetrabenazine dosing is titration-sensitive; documentation of AIMS response plus mood and QT-related safety supports both clinical decisions and payer renewals.

Adverse Effects

Interactions

• Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) increase exposure—limit dose to 36 mg/day and monitor QTc and sedation.
• Contraindicated with MAOIs, tetrabenazine, or reserpine due to excessive monoamine depletion.
• Additive sedation with alcohol, benzodiazepines, opioids, or other CNS depressants increases fall risk; fall-risk counseling is common.
• Caution is warranted with QT-prolonging antipsychotics (ziprasidone, haloperidol, methadone); ECG monitoring may be considered.

Other Useful Information

• Tardive dyskinesia severity (AIMS or equivalent) at baseline and follow-up visits to document benefit.
• Mood changes, depression, or suicidality are screened for at each encounter; caregivers are involved when available.
• Baseline hepatic function is typically checked (therapy contraindicated in hepatic impairment), and baseline ECG is often considered in patients with cardiac risk factors or when using CYP2D6 inhibitors.
• Doses are taken with food to improve absorption and reduce gastrointestinal upset; XR tablet shells may pass in stool.

References

1. AUSTEDO (deutetrabenazine) prescribing information — DailyMed (2025)
2. Anderson2017 AIM TD
3. Brar JS et al. Pharmacokinetic characterization of deutetrabenazine and valbenazine.