Role of Tetrabenazine for Huntington's Disease-Associated Chorea

• Published in: The Annals of pharmacotherapy 2010-06, Vol.44 (6), p.1080-1089
• Main Authors: Poon, Linda H, Kang, Gail A, Lee, Audrey J
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Biological and medical sciences; Clinical Trials as Topic - methods; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Huntington Disease - drug therapy; Huntington Disease - metabolism; Medical sciences; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Organic mental disorders. Neuropsychology; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - metabolism; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Sleep Stages - drug effects; Sleep Stages - physiology; Tetrabenazine - adverse effects; Tetrabenazine - chemistry; Tetrabenazine - therapeutic use
• ISSN: 1060-0280; 1542-6270
• DOI: 10.1345/aph.1M582

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of saxagliptin, a new dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes. Data Sources: Primary literature and review articles were obtained through a PubMed search (1959–November 2009) using the terms tetrabenazine, HD, chorea, and hyperkinetic movement disorders. A bibliographic search was performed on selected articles. Study Selection and Data Extraction: Alt English-language articles identified from the data sources were reviewed. Studies including greater than 10 patients and a direct comparative study with primarily HD-associated chorea were included in the review. Data Synthesis: Tetrabenazine is the first drug approved by the Food and Drug Administration (FDA) for the management of HD-associated chorea. Tetrabenazine binds reversibly to the type 2 vesicular monoamine transporters and has been shown to inhibit monoamine uptake in presynaptic vesicles, resulting in monoamine depletion. The duration of the antichorea effect of tetrabenazine has been reported to be approximately 5.5 hours. Tetrabenazine is extensively metabolized hepatically by the CYP2D6 enzyme to its primary active metabolite, alpha-dihydrotetrabenazine. The half-life of alpha-dihydrotetrabena-zine is 4-8 hours. Clinical trials demonstrated that tetrabenazine reduces chorea, on average, by 5 units based upon the chorea score from the Unified Huntington's Disease Rating Scale. The most common adverse effects reported include sedation, drowsiness, parkinsonism, and depression. Rarely, corrected QT interval prolongation, orthostatic hypotension, and hyperprolactinemia have been reported. Tetrabenazine also has a black box warning for increasing the risk of depression and suicidally Conclusions: Tetrabenazine can provide significant benefit in the treatment of chorea associated with HD. Given the potential adverse effects of tetrabenazine, health-care providers need to screen patients carefully prior to initiating treatment with this medication. In the future, additional long-term and comparative studies would be useful for further clarification of the role of tetrabenazine in the treatment of HD-associated chorea.