Tetrabenazine is a reversible, centrally acting inhibitor of the vesicular monoamine transporter type 2 (VMAT2). It depletes presynaptic dopamine, serotonin, norepinephrine, and histamine stores in the central nervous system. It is specifically indicated for the treatment of chorea associated with Huntington's disease (HD). In the Indian context, it is a critical drug for managing a debilitating symptom of a rare neuropsychiatric disorder, requiring careful titration and monitoring due to its narrow therapeutic index and significant side effect profile.
Adult: Initial: 12.5 mg once daily. Titrate slowly: Increase by 12.5 mg increments at weekly intervals. Usual therapeutic dose: 25-50 mg/day in 2-3 divided doses. Maximum single dose: 25 mg. Must be individualized based on response and tolerability.
Note: Administer with food to minimize gastrointestinal upset. Tablets can be swallowed whole with water. Dosing should be divided (e.g., twice or thrice daily) to maintain stable levels and minimize peak-dose side effects.
Tetrabenazine binds reversibly and with high affinity to the Vesicular Monoamine Transporter 2 (VMAT2) on presynaptic vesicles in neurons. This binding inhibits the uptake of monoamines (dopamine, serotonin, norepinephrine, histamine) from the cytoplasm into synaptic vesicles, preventing their storage and subsequent release into the synaptic cleft. The cytoplasmic monoamines are then degraded by monoamine oxidases (MAO). The net effect is a profound and selective depletion of monoamines, particularly dopamine, in the basal ganglia, which is central to its anti-chorea effect in Huntington's disease.
Pregnancy: Category C: Animal studies show teratogenicity. No adequate human studies. Use only if potential benefit justifies potential fetal risk. Consider discontinuing if pregnancy is planned or detected.
Driving: May impair alertness, judgment, and motor coordination. Patients should not drive or operate heavy machinery until they know how the drug affects them, especially during dose titration.
| Monoamine Oxidase Inhibitors (MAOIs) - e.g., Phenelzine, Selegiline, Moclobemide | Risk of severe serotonin syndrome and hypertensive crisis. | Contraindicated |
| Strong CYP2D6 Inhibitors - e.g., Paroxetine, Fluoxetine, Quinidine, Bupropion | Markedly increases tetrabenazine active metabolite levels, increasing risk of side effects (sedation, QT prolongation). | Major - Dose reduction of tetrabenazine required. |
| Antipsychotics (e.g., Haloperidol, Risperidone, Olanzapine) | Additive risk of sedation, parkinsonism, akathisia, and QTc prolongation. | Major |
| Alcohol and CNS Depressants (e.g., Benzodiazepines, Opioids) | Additive CNS depression and sedation. | Moderate |
| Drugs that prolong QTc (e.g., Class IA/III antiarrhythmics, certain antibiotics, methadone) | Additive risk of QTc prolongation and cardiac arrhythmias. | Major |
| Levodopa and Dopamine Agonists | Pharmacological antagonism; may reduce efficacy of dopaminergic therapy. | Moderate |