Tetrabenazine for the treatment of hyperkinetic movement disorders: a review of the literature.

Abstract

BACKGROUND:

Tetrabenazine (TBZ) is a monoamine storage inhibitor that was first introduced in the 1970s for the management of hyperkinetic movement disorders. Despite acceptance and usage worldwide, TBZ was only recently approved in the United States for the treatment of Huntington chorea. This review focuses on the use of TBZ in various hyperkinetic movement disorders, which are considered "rare" or "orphan" diseases, to help practitioners better understand its clinical role and use.

OBJECTIVE:

This review describes the clinical efficacy and tolerability of TBZ in the management of dystonia, Huntington chorea, tardive dyskinesia (TDk), and tic disorders.

METHODS:

A Cochrane Library, EMBASE, MedlinePlus, PubMed, and clinical trials database search (up to May 2012) was conducted to identify articles and studies using the subject terms tetrabenazine, Huntington disease, dystonia, tardive dyskinesia, Tourette, tics, and hyperkinetic movement. Only English-language articles were reviewed.

RESULTS:

TBZ variably undergoes extensive first-pass metabolism to active metabolites, some of which are metabolized by the cytochrome P450 2D6 isozyme. Pharmacology studies demonstrate that TBZ reversibly inhibits the activity of vesicular monoamine transporter 2, resulting in depletion of central dopamine. For management of dystonias, 1 of 3 small prospective blinded studies and 4 of 5 retrospective studies reported clinical benefit with TBZ use in pediatrics and adults. For Huntington chorea, 2 randomized, double-blind, placebo-controlled studies along with open-label studies demonstrate the effectiveness of TBZ in adults. For TDk, 9 of 11 studies (prospective controlled and retrospective) reported positive benefit. For Gilles de la Tourette syndrome, 9 of 11 studies (prospective controlled and retrospective) reported positive benefit on motor and phonic tics in pediatric and adult patients. Overall, adverse effects are dose and age related and include depression, fatigue, parkinsonism, and somnolence.

CONCLUSIONS:

TBZ is an effective oral therapy for chorea of Huntington disease and may be considered as an alternative agent for the management of dystonia, TDk, and tic disorders (these latter 3 conditions are off-label uses in the United States). The drug possesses an acceptable tolerability profile and has been used in pediatric and adult populations.

• Authors: Jack J Chen, William G Ondo, Khashayar Dashtipour, David M Swope
• Journal: Clinical therapeutics (Clin Ther) Vol. 34 Issue 7 Pg. 1487-504 (Jul 2012) ISSN: 1879-114X [Electronic] United States
• PMID: 22749259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Chemical References

• Adrenergic Uptake Inhibitors
• Tetrabenazine

Topics

• Adrenergic Uptake Inhibitors (adverse effects, pharmacology, therapeutic use)
• Animals
• Chorea (drug therapy, physiopathology)
• Dystonia (drug therapy, physiopathology)
• Humans
• Huntington Disease (drug therapy, physiopathology)
• Hyperkinesis (drug therapy, physiopathology)
• Movement Disorders (drug therapy, physiopathology)
• Rare Diseases (drug therapy, physiopathology)
• Tetrabenazine (adverse effects, pharmacology, therapeutic use)
• Tic Disorders (drug therapy, physiopathology)