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Treatment of Tardive Dyskinesia: A General Overview with Focus on the Vesicular Monoamine Transporter 2 Inhibitors

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A Correction to this article was published on 10 March 2018

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Abstract

Tardive dyskinesia (TD) encompasses the spectrum of iatrogenic hyperkinetic movement disorders following exposure to dopamine receptor-blocking agents (DRBAs). Despite the advent of atypical or second- and third-generation antipsychotics with a presumably lower risk of complications, TD remains a persistent and challenging problem. Prevention is the first step in mitigating the risk of TD, but early recognition, gradual withdrawal of offending medications, and appropriate treatment are also critical. As TD is often a persistent and troublesome disorder, specific antidyskinetic therapies are often needed for symptomatic relief. The vesicular monoamine transporter 2 (VMAT2) inhibitors, which include tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice for most patients with TD. Deutetrabenazine—a deuterated version of tetrabenazine—and valbenazine, the purified parent product of one of the main tetrabenazine metabolites, are novel VMAT2 inhibitors and the only drugs to receive approval from the US FDA for the treatment of TD. VMAT2 inhibitors deplete presynaptic dopamine and reduce involuntary movements in many hyperkinetic movement disorders, particularly TD, Huntington disease, and Tourette syndrome. The active metabolites of the VMAT2 inhibitors have high affinity for VMAT2 and minimal off-target binding. Compared with tetrabenazine, deutetrabenazine and valbenazine have pharmacokinetic advantages that translate into less frequent dosing and better tolerability. However, no head-to-head studies have compared the various VMAT2 inhibitors. One of the major advantages of VMAT2 inhibitors over DRBAs, which are still being used by some clinicians in the treatment of some hyperkinetic disorders, including TD, is that they are not associated with the development of TD. We also briefly discuss other treatment options for TD, including amantadine, clonazepam, Gingko biloba, zolpidem, botulinum toxin, and deep brain stimulation. Treatment of TD and other drug-induced movement disorders must be individualized and based on the severity, phenomenology, potential side effects, and other factors discussed in this review.

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  • 10 March 2018

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No sources of funding were used to conduct this study or prepare this manuscript.

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  1. Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, 7200 Cambridge, Suite 9A, Houston, TX, 77030, USA

    Nicki Niemann & Joseph Jankovic

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  1. Nicki Niemann
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NN contributed to the conception, design, organization, and execution of the study and the writing of the first and subsequent drafts. JJ contributed to the conception, design, organization, and execution of the study, to review and critique, and to writing of the second and subsequent drafts.

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Correspondence to Joseph Jankovic.

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Conflict of interest

Nicki Niemann has no conflicts of interest that are directly relevant to the content of this study. Dr. Jankovic has received research and/or training grants from Adamas Pharmaceuticals, Inc.; Allergan, Inc.; Biotie Therapies; CHDI Foundation; Civitas/Acorda Therapeutics; Dystonia Coalition; Dystonia Medical Research Foundation; F. Hoffmann-La Roche Ltd; Huntington Study Group; Kyowa Haako Kirin Pharma, Inc.; Medtronic Neuromodulation; Merz Pharmaceuticals; Michael J. Fox Foundation for Parkinson Research; National Institutes of Health; Neurocrine Biosciences; NeuroDerm Ltd; Parkinson’s Foundation; Nuvelution; Parkinson Study Group; Pfizer Inc.; Prothena Biosciences Inc.; Psyadon Pharmaceuticals, Inc.; Revance Therapeutics, Inc.; Sangamo BioSciences, Inc.; St. Jude Medical; and Teva Pharmaceutical Industries Ltd. Dr. Jankovic has served as a consultant or as an advisory committee member for Adamas Pharmaceuticals, Inc.; Allergan, Inc.; Merz Pharmaceuticals; Pfizer Inc.; Prothena Biosciences; Revance Therapeutics, Inc.; and Teva Pharmaceutical Industries Ltd. Dr. Jankovic has also received royalties or other payments from Cambridge; Elsevier; Future Science Group; Hodder Arnold; Medlink: Neurology; Lippincott Williams and Wilkins; and Wiley-Blackwell.

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The original version of this article was revised: Due to Figure 1 update.

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Niemann, N., Jankovic, J. Treatment of Tardive Dyskinesia: A General Overview with Focus on the Vesicular Monoamine Transporter 2 Inhibitors. Drugs 78, 525–541 (2018). https://doi.org/10.1007/s40265-018-0874-x

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