Makindo Medical Notes

Tetrabenazine is a monoamine-depleting drug used to suppress hyperkinetic movement disorders such as chorea, hemiballismus, and severe tardive dyskinesia. It acts by reducing dopaminergic tone in the basal ganglia. It should be prescribed only by clinicians experienced in movement disorder management. Always 🔗 check the BNF entry for current dosing, cautions, and interactions.

⚙️ Mode of Action

• Reversibly inhibits the vesicular monoamine transporter type 2 (VMAT2) in presynaptic neurons.
• This prevents dopamine, noradrenaline, and serotonin from being packaged into synaptic vesicles → cytosolic depletion of monoamines.
• As dopamine is reduced in basal ganglia synapses, the excessive motor drive seen in chorea and tics is dampened.
• Mechanistically similar in end-effect to reserpine, but shorter-acting and more titratable.

💊 Indications / Typical Doses

• Chorea (e.g. Huntington’s disease, hemiballismus): Start 12.5 mg once or twice daily, increase gradually to 25 mg TDS as tolerated (max 200 mg/day).
• Tardive dyskinesia (severe cases): Start 12.5 mg OD; increase slowly as tolerated. Lower maximum dose in elderly or frail patients.
• Administer with food to reduce gastrointestinal effects.
• Monitor mental health at each dose increment — depression and suicidality are dose-related risks.

⚠️ Pharmacology Notes

• Onset: Within a few days; maximal effect after several weeks.
• Half-life: 4–8 hours (shorter than reserpine).
• Metabolism: Hepatic via CYP2D6 to active metabolites → dose adjustment needed in poor metabolisers or when on CYP2D6 inhibitors (e.g. fluoxetine, paroxetine).
• Elimination: Renal and faecal routes.

🔄 Interactions

• QT-prolonging drugs: macrolides, quinolones, antipsychotics, tricyclics — ↑ risk of arrhythmia.
• MAO inhibitors: contraindicated — risk of serotonin or hypertensive crisis.
• Antidepressants (SSRIs, TCAs): increase risk of sedation and serotonergic imbalance.
• Dopaminergic agents (e.g. levodopa, dopamine agonists): antagonised by tetrabenazine.

🚧 Cautions

• QT prolongation: baseline and periodic ECG advised, especially with interacting drugs.
• Depression and suicidality: screen before and during treatment — consider dose reduction or withdrawal if mood worsens.
• Parkinsonism: may unmask or worsen bradykinesia and rigidity.
• Hepatic impairment: reduced clearance — use lower starting dose and slow titration.
• Elderly: more sensitive to sedation and hypotension.

⛔ Contraindications

• Active or untreated depression or history of suicidal ideation.
• Parkinson’s disease or Parkinsonian syndromes.
• Phaeochromocytoma (may precipitate hypertensive crisis).
• Prolactinoma or prolactin-dependent malignancy (drug increases prolactin levels).
• Severe hepatic impairment.

💢 Side Effects

• CNS: drowsiness, confusion, anxiety, insomnia, depression, suicidal ideation.
• Neurological: Parkinsonism, dystonia, akathisia, neuroleptic malignant syndrome (rare).
• Autonomic: postural hypotension, bradycardia, dizziness.
• Metabolic: weight loss, GI upset, fatigue.

🧮 Monitoring

• Monitor mental state and screen for depression at baseline and every review.
• Check ECG at baseline and during dose escalation if on QT-prolonging drugs.
• Observe for early signs of Parkinsonism or rigidity — reduce dose if seen.
• Monitor BP, mood, and extrapyramidal symptoms at each visit.

🧠 Clinical Pearls

• Tetrabenazine is particularly valuable in Huntington’s disease chorea where dopaminergic overactivity drives involuntary movement.
• Psychiatric monitoring is critical — depressive symptoms may emerge even after months of stability.
• For treatment-resistant tardive dyskinesia, newer VMAT2 inhibitors (e.g. deutetrabenazine) offer longer half-life and fewer mood effects (not yet widely used in UK).
• If sedation or parkinsonism develops, reduce dose or divide more frequently (e.g. 12.5 mg QDS instead of 25 mg TDS).

📚 References

• BNF: Tetrabenazine
• Nice CKS: Movement disorders – Huntington’s and chorea.
• MHRA Drug Safety Update (2023): VMAT2 inhibitors – psychiatric risk monitoring.
• UpToDate: Management of chorea and tardive dyskinesia.