Pharmacology · VMAT2 inhibitors
Tetrabenazine !
A VMAT2 inhibitor that depletes dopamine to control Huntington chorea. It can cause depression, suicidality and parkinsonism.
Updated 2026-11-01
The figure shows tetrabenazine bound to human VMAT2.
Mechanism of action
Tetrabenazine reversibly inhibits VMAT2, so monoamines (dopamine, serotonin, noradrenaline, histamine) are not packed into vesicles and are degraded in the cytoplasm. Depleting striatal dopamine reduces the involuntary movements of chorea. Its active dihydro-metabolites are made and cleared through CYP2D6.
- Tetrabenazine blocks VMAT2 on synaptic vesicles
- Dopamine stays in the cytoplasm and is broken down
- Less dopamine is released in the striatum
- Choreic movements decrease
Pharmacokinetics
- Metabolism
- Extensive first-pass conversion to active dihydrotetrabenazines, cleared by CYP2D6
Indications
- Chorea of Huntington disease Huntington disease →
- Tardive dyskinesia and other hyperkinetic disorders (specialist, off-label in some countries) Antipsychotic-induced movement disorders (dystonia, akathisia, parkinsonism, tardive dyskinesia) →
Adverse effects
Common
- Sedation and somnolence
- Fatigue and insomnia
- Akathisia, restlessness and anxiety
- Nausea
Contraindications
- Active suicidality, or untreated or undertreated depression
- Liver impairment
- MAO inhibitors (and within 14 days of stopping them)
- Reserpine (at least 20 days must pass after stopping it)
- Deutetrabenazine or valbenazine
Key interactions
- Strong CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine)
- Higher active metabolite levels; dose is reduced
- Drugs that prolong QT
- Additive QT prolongation; avoided
- Antipsychotics and other dopamine antagonists
- More parkinsonism, NMS and QT risk
- Alcohol and sedatives
- More sedation
What is monitored
- Mood, depression and suicidal thoughts at every visit
- Parkinsonism, akathisia and swallowing
- ECG when QT risk factors are present
- CYP2D6 genotype when higher doses are needed
Administration and safety
- Increased slowly, week by week, according to response and adverse effects
- Not given with or soon after MAO inhibitors or reserpine
- Look-alike names: tetrabenazine, deutetrabenazine, valbenazine are not interchangeable
Nursing care
- Screen for depression and suicidal thoughts; involve the family
- Watch for stiffness, slowness, restlessness and swallowing problems
- Warn about drowsiness and alcohol
- Report fever with rigidity or confusion urgently (NMS)
Pregnancy and breastfeeding
There are no adequate human data; in rats it increased stillbirths and offspring deaths.
Test yourself
Think of the answer, then tap the question to see it.
Which transporter does tetrabenazine inhibit?
VMAT2, the vesicular monoamine transporter 2.
Which psychiatric conditions contraindicate tetrabenazine?
Active suicidality and untreated or inadequately treated depression.
Which genetic test can guide higher doses of tetrabenazine?
CYP2D6 genotyping (poor versus extensive metabolizers).
Related drugs
Related conditions
- Huntington disease
- Antipsychotic-induced movement disorders (dystonia, akathisia, parkinsonism, tardive dyskinesia)
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - TETRABENAZINE tablet (DailyMed (U.S. National Library of Medicine), 2026); Tetrabenazine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2018); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023).
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Representative model, for educational purposes only.