In August 2008, tetrabenazine was approved by the FDA for the treatment of movement disorders associated with Huntington’s disease.23 It has also been investigated as a possible treatment for antipsychotic-associated tardive dyskinesia and other hyperkinetic movement disorders.44 In the case of tetrabenazine, pharmacogenomic testing could be highly relevant since the parent drug and its equivalently active metabolites are primarily metabolized by CYP2D6.45 In the initially approved labeling, genetic testing information was included with the recommendation that genetic testing for CYP2D6 be completed prior to the initiation of the tetrabenazine treatment with daily doses exceeding 50 mg.23 This information appears to be based on a small number (n=2) of PMs profiled in pharmacokinetic studies during drug development, with further justification from pharmacologic CYP2D6 drug inhibition studies. These studies suggest robust differences in the pharmacokinetics of the drug in PMs. A subsequent investigation that included adverse-effect assessments identified trends suggesting more adverse events (i.e., sedation, akathisia, insomnia, and suicidality) in PMs.45 Although not statistically significant, they may still be clinically meaningful. The adverse events experienced included drowsiness, akathisia, parkinsonism, confusion, and depression.
