Role of tetrabenazine for Huntington's disease-associated chorea.
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Poon LH, Kang GA, Lee AJ
Role of tetrabenazine for Huntington's disease-associated chorea.
Ann Pharmacother. 2010 Jun;44(6):1080-9. doi: 10.1345/aph.1M582. Epub 2010 May 4.
- PubMed ID
- 20442355 [ View in PubMed]
- Abstract
OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of tetrabenazine for the treatment of Huntington's disease (HD)-associated chorea. 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: All 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-dihydrotetrabenazine 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 suicidality. 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Tetrabenazine Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareDeutetrabenazineMoricizine The risk or severity of adverse effects can be increased when Moricizine is combined with Deutetrabenazine. DeutetrabenazineAlimemazine The risk or severity of adverse effects can be increased when Alimemazine is combined with Deutetrabenazine. DeutetrabenazineLithium cation The risk or severity of adverse effects can be increased when Lithium cation is combined with Deutetrabenazine. DeutetrabenazineOsanetant The risk or severity of adverse effects can be increased when Osanetant is combined with Deutetrabenazine. DeutetrabenazineBifeprunox The risk or severity of adverse effects can be increased when Bifeprunox is combined with Deutetrabenazine.