Analysis of CYP2D6 genotype and response to tetrabenazine

Authors

  • Raja Mehanna MD,

    1. Parkinson's Disease Center, Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
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  • Christine Hunter RN,

    1. Parkinson's Disease Center, Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
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  • Anthony Davidson MS,

    1. Parkinson's Disease Center, Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
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  • Joohi Jimenez-Shahed MD,

    1. Parkinson's Disease Center, Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
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  • Joseph Jankovic MD

    Corresponding author
    1. Parkinson's Disease Center, Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
    • Correspondence to: Dr. Joseph Jankovic, Professor of Neurology, Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, TX 77030, USA; josephj@bcm.edu

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  • Funding agencies: This study was partially funded by lundbeck.

  • Relevant conflicts of interest/financial disclosures: Christine Hunter has received consulting fees from Lundbeck for patient education. Joohi Jimenez-Shahed has received honoraria and consulting fees from Lundbeck. Joseph Jankovic has received research grants and consulting fees from Lundbeck.

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Tetrabenazine is effective in the treatment of the chorea associated with Huntington disease and other hyperkinetic movement disorders. Following oral administration, tetrabenazine is hepatically transformed into 2 active metabolites that are CYP2D6 substrates. There are 4 CYP2D6 genotypes: poor metabolizers, intermediate metabolizers, extensive metabolizers, and ultrarapid metabolizers. CYP2D6 genotyping was performed on sequential subjects treated with tetrabenazine, but results were not known at the time of titration. Duration of titration to a stable dose, total daily dose, response rating scores, and adverse events were retrospectively collected and subsequently analyzed. Of 127 patients, the majority (n = 100) were categorized as extensive metabolizers, 14 as intermediate metabolizers, 11 as poor metabolizers, and 2 as ultrarapid metabolizers. Ultrarapid metabolizer patients needed a longer titration (8 vs 3.3, 4.4, and 3 weeks, respectively; P < .01) to achieve optimal benefit and required a higher average daily dose than the other patients, but this difference did not reach statistical significance. The treatment response was less robust in the intermediate metabolizer group when compared with the extensive metabolizer patients (P = .013), but there were no statistically significant differences between the various groups with regard to adverse effects. Our findings demonstrate that, aside from the need for a longer titration in the ultrarapid metabolizers, there are no distinguishing features of patients with various CYP2D6 genotypes, and therefore the current recommendation to systematically genotype all patients prescribed more than 50 mg/day of tetrabenazine should be reconsidered. © 2012 Movement Disorder Society

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