Tetrabenazine for treatment of chorea associated with Huntington's disease and other potential indications

Introduction: Tetrabenazine (TBZ) is a centrally acting, dopamine (DA) depleting drug that has been used for treatment of hyperkinetic movement disorders. It was not commercially available in the USA until 2008, when the Food and Drug Administration (FDA) approved TBZ for the management of chorea associated with Huntington's disease (HD) under an orphan drug designation. Areas covered: This article provides a brief overview of HD, and highlights key studies on pharmacodynamics, pharmacokinetics, clinical efficacy and safety of TBZ for treatment of HD chorea. Expert opinion: TBZ, the first FDA-approved therapy for HD, provides symptomatic relief of chorea but there is no evidence that it alters the natural course of HD through a disease-modifying effect. While sedation, insomnia, mood changes, parkinsonism and restlessness may occur, these adverse effects can be managed effectively with appropriate titration and monitoring. A black box warning against depression and suicidality warrants careful patient selection, close monitoring and judicious use of antidepressants. TBZ possesses a unique mechanism of action as a pre-synaptic DA depletor that offers possible advantages over DA receptor blocking drugs. TBZ has a strong potential for application in other hyperkinetic movement disorders, particularly tardive dyskinesia and Tourette syndrome, but randomized controlled clinical trials are lacking.