I read with interest the recent guideline on the treatment of chorea in Huntington disease¹ and the recommendation of using up to 100 mg of tetrabenazine daily. The authors reviewed side effects of this medication including parkinsonism and depression. However, they did not mention that tetrabenazine is metabolized by cytochrome P450 (CYP2D6). Care needs to be taken when tetrabenazine is used with antidepressants such as paroxetine and fluoxetine and other drugs that are inhibitors of CYP2D6. Because individuals with Huntington disease are often treated with these antidepressants, the dose of tetrabenazine should be decreased by 50%.² Secondly, some individuals metabolize tetrabenazine faster than others. If doses more than 50 mg per day are being considered, it is recommended that patients undergo testing for CYP2D6 metabolizer status to determine whether they are slow metabolizers.³ Dosages above 50 mg per day in both of these circumstances will increase the risk of side effects.

Author Response

We thank Dr. Suchowersky for her comments on the treatment of chorea in Huntington disease guideline.¹ Although we did not address tetrabenazine (TBZ) metabolism in the evidence section of the guideline text, we did refer to this in the clinical context: “US TBZ prescribing information recommends genotyping for CYP2D6, the enzyme responsible for metabolizing TBZ, prior to TBZ use. Whether this advice is followed clinically is unknown. Possible interactions with other medications metabolized by the CYP2D6 system, such as fluoxetine or paroxetine, should be considered during TBZ dosing.” The American Academy of Neurology guideline development process is intended to provide a formal assessment of the strength of the evidence in response to a specific question and cannot serve as the sole reference for clinicians considering prescribing any particular agent. Dosing recommendations are based on the evidence formally reviewed. Thus, some details—such as those mentioned by Dr. Suchowersky—cannot be fully captured in guideline publications. We agree with her points and encourage clinicians to consult prescribing information and other resources before choosing the best approach and dosage for their individual patients.