Drug Evaluation

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

*Author for correspondence:

E-mail Address: sfrank2@bidmc.harvard.edu

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

Published Online:9 Jan 2019https://doi.org/10.2217/nmt-2018-0040

Abstract

Deutetrabenazine (DTBZ) is a US FDA-approved treatment for chorea in Huntington's disease. The substitution of deuterium for hydrogen at specific positions imparts a longer half-life on DTBZ, allowing for less-frequent daily dosing. As a reversible vesicular monoamine transporter Type 2 inhibitor, DTBZ depletes monoamines at presynaptic nerve terminals. DTBZ significantly improved chorea in Huntington's disease patients compared with placebo. This effect continued in an ongoing open-label extension study in the cohort who switched from tetrabenazine to DTBZ. Whereas there are currently no head-to-head studies to adequately compare safety profiles between tetrabenazine and DTBZ, an indirect comparison study suggested that the tolerability profile of DTBZ was similar to placebo. In fact, there are currently no direct comparisons between vesicular monoamine transporter Type 2 inhibitors in humans. This review will explore DTBZ's pharmacological properties, drug interactions, administration and efficacy.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1 Dean M, Sung VW, Heo YA et al. Safety of converting from tetrabenazine to deutetrabenazine for the treatment of Chorea. Drugs doi:10.1007/s40265-017-0831-0 (2017) (Epub ahead of print).
Google Scholar
2 Niemann N, Jankovic J. Treatment of tardive dyskinesia: a general overview with focus on the vesicular monoamine transporter 2 inhibitors. Drugs doi:10.1007/s40265-018-0874-x (2018) (Epub ahead of print).
Google Scholar
3 Roos R. Huntington's Disease: A Clinical Review. 5, doi:10.1186/1750-1172-5-40 (2010) (Epub ahead of print).
Google Scholar
4 Zielonka D. Factors contributing to clinical picture and progression of Huntington's disease. Neural Regen. Res. 13(8), 1364 (2018).
MedlineGoogle Scholar
5 Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C. Therapeutic interventions for symptomatic treatment in Huntington's disease. Cochrane Database Syst Rev. (3), (doi:10.1002/14651858.CD006456.pub2 (2009) (Epub ahead of print).• Good and recent review on the symptomatic management of Huntington's disease (HD).
Google Scholar
6 Heo YA, Scott LJ. Deutetrabenazine: a review in chorea associated with Huntington's disease. Drugs doi:10.1007/s40265-017-0831-0 (2017) (Epub ahead of print).
Google Scholar
7 McColgan P, Tabrizi SJ. Huntington's disease: a clinical review. Eur. J. Neurol. 25(1), 24–34 (2018).
Medline CASGoogle Scholar
8 Coppen EM, Roos RAC. Current pharmacological approaches to reduce chorea in Huntington's disease. Drugs 77(1), 29–46 (2017).
Medline CASGoogle Scholar
9 Frank S. Treatment of Huntington's Disease. Neurotherapeutics doi:10.1007/s13311-013-0244-z (2014) (Epub ahead of print).
MedlineGoogle Scholar
10 Burgunder J-M, Guttman M, Perlman S, Goodman N, van Kammen DP, Goodman L. An international survey-based algorithm for the pharmacologic treatment of chorea in Huntington's disease. PLoS Curr. 3, RRN1260 (2011).
MedlineGoogle Scholar
11 Citrome L. Deutetrabenazine for tardive dyskinesia: a systematic review of the efficacy and safety profile for this newly approved novel medication – what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int. J. Clin. Pract. 71(11), 1–17 (2017).
Google Scholar
12 Frank S, Stamler D, Kayson E et al. Safety of converting from tetrabenazine to deutetrabenazine for the treatment of Chorea. JAMA Neurol. doi:10.1001/jamaneurol.2017.1352 (2017) (Epub ahead of print).• Relevant article about how to convert tetrabenazine to deutetrabenazine along with valuable practice points.
MedlineGoogle Scholar
13 Stamler D, Bradbury M, Brown F. The pharmacokinetics and safety of deuterated-tetrabenazine (P07.210). Neurology. 80(7 Suppl.), P07.210 LP–P07.210 (2013).
Google Scholar
14 Stamler D, Bradbury M, De Boer L, Offman E. A relative bioavailability study of three dose strengths and four dose levels of SD-809, a potential treatment for movement disorders. In: Neurology 86, P1.054 (2016) (Accessed 25 September 2018).
Google Scholar
15 Jankovic J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opin. Pharmacother. 17(18), 2461–2470 (2016).
Medline CASGoogle Scholar
16 Timmins GS. Deuterated drugs: where are we now? Expert Opin. Ther. Pat. 24(10), 1067–1075 (2014).
Medline CASGoogle Scholar
17 Geschwind MD, Paras N. Deutetrabenazine for treatment of chorea in huntington disease. JAMA 316(1), 33 (2016).
Medline CASGoogle Scholar
18 Guengerich FP. Kinetic deuterium isotope effects in cytochrome p450 oxidation reactions. J. Label Compd. Radiopharm. 56(9–10), 428–431 (2013).
Medline CASGoogle Scholar
19 Timmins GS. Deuterated drugs; updates and obviousness analysis. Expert Opin. Ther. Pat. 27(12), 1353–1361 (2017).
Medline CASGoogle Scholar
20 Huntington Study Group. Effect of deutetrabenazine on chorea among patients with Huntington disease. JAMA 316(1), 40 (2016). •• The FIRST-HD trial highlighted in this article.
MedlineGoogle Scholar
21 Dean M, Sung VW. Review of deutetrabenazine: a novel treatment for chorea associated with Huntington's disease. Drug Des. Devel. Ther. 12, 113–319 (2018).
Google Scholar
22 Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology 66(3), 366–372 (2006). •• The TETRA-HD trial highlighted in this article.
MedlineGoogle Scholar
23 Frank S. Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators. BMC Neurol. doi:10.1186/1471-2377-9-62 (2009) (Epub ahead of print).
MedlineGoogle Scholar
24 Huntington Study Group. Alternatives for reducing chorea in Huntington disease, a long-term trial (ARC-HD): updated week 8 results for the switch cohort [abstract]. Mov. Disord. 31(2), Abstract 1145 (2016).
Google Scholar
25 Rodrigues F, Duarte G, Costa J, Ferreira J, Wild E. Tetrabenazine versus deutetrabenazine for Huntington's disease: twins or distant cousins? Mov. Disord. Clin. Pract. doi:10.1002/mdc3.12483 (2017) (Epub ahead of print).
Google Scholar
26 Claassen DO, Carroll B, De Boer LM et al. Indirect tolerability comparison of deutetrabenazine and tetrabenazine for Huntington disease. J. Clin. Mov. Disord. doi:10.1186/s40734-017-0051-5 (2017) (Epub ahead of print).
MedlineGoogle Scholar
27 Rodrigues F, Duarte GS, Costa J, Ferreira JJ, Wild EJ. Meta-research metrics matter: letter regarding article “indirect tolerability comparison of deutetrabenazine and tetrabenazine for Huntington disease”. J. Clin. Mov. Disord. 4(1), 19 (2017). • Relevant commentary to reconcile the apparent difference between the two indirect comparison studies of tetrabenazine and deutetrabenazine.
MedlineGoogle Scholar
28 Reilmann R. Deutetrabenazine – not a revolution but welcome evolution for treating chorea in Huntington disease. JAMA Neurol. 73(12), 1404 (2016).
MedlineGoogle Scholar

Vol. 9, No. 1

Metrics

Downloaded 220 times

History

Received 10 October 2018

Accepted 3 December 2018

Published online 9 January 2019

Published in print February 2019

Information

Keywords

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

PDF download

Deutetrabenazine in the treatment of Huntington's disease

Abstract

References