Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders

Abstract

Tetrabenazine (TBZ; Xenazine^®) is a potent, selective, reversible depletor of monoamines from nerve terminals. TBZ inhibits the vesicular monoamine transporter type 2 which, in humans, is expressed nearly exclusively in the brain. TBZ is rapidly metabolized in the liver by carbonyl reductase to stereoisomers of hydrotetrabenazine, some of which are potent inhibitors of vesicular monoamine transporter type 2. Initially developed in the 1950s for schizophrenia, since the 1970s several publications have reported on the efficacy of TBZ in the treatment of various hyperkinetic movement disorders. Although quite effective in controlling the involuntary movements, there were considerable inter-individual differences in the optimal dose, defined as the dose judged by the investigator to provide the greatest efficacy with minimal or tolerable adverse events. This variability is in part owing to differences in severity and mechanism of the target symptoms and to variable activity of the enzyme carbonyl reductase that metabolizes TBZ to its active metabolites. Dose-limiting adverse events, consisting mainly of sedation, parkinsonism, akathisia and depression, are usually rapidly reversible upon dosage reduction. In addition to its established antichorea efficacy in Huntington’s disease, the drug has been reported to also be effective in a variety of other hyperkinetic movement disorders, including tardive dyskinesia and tics associated with Tourette’s syndrome.

Keywords::

• chorea
• Huntington’s disease
• tardive dyskinesia
• tetrabenazine
• Tourette’s syndrome
• VMAT2 inhibition

Acknowledgements

We thank Jeanna Donahue and Jen Feranil for their editorial assistance.

Financial & competing interests disclosure

Kathleen Clarence-Smith was employed by Prestwick Pharmaceuticals and is a paid consultant to Lundbeck Inc., which markets tetrabenazine (Xenazine^®) in the USA. Joseph Jankovic has received research grants and consultation fees from Lundbeck Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.