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Tardive Dyskinesia: Therapeutic Options for an Increasingly Common Disorder

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  • Published:
Neurotherapeutics

Abstract

Tardive dyskinesia (TD) is a serious, often disabling, movement disorder that is caused by medications that block dopamine receptors (i.e., neuroleptics, anti-emetics). There is currently no standard treatment approach for physicians confronted with such patients. This may be the result of notions that TD is disappearing because of the switch to second-generation antipsychotic agents and that it is largely reversible. In this article we demonstrate that second-generation antipsychotics do, indeed, cause TD and, in fact, the frequency is likely higher than expected because of growing off-label uses and a tripling of prescriptions written in the last 10 years. In addition, studies demonstrate that TD actually remits in only a minority of patients when these drugs are withdrawn. Furthermore, neuroleptic agents are often utilized to treat TD, despite prolonged exposure being a risk factor for irreversibility. The outcome of these trends is a growing population afflicted with TD. We review non-neuroleptic agents that have shown positive results in small, early-phase, blinded trials, including tetrabenazine, amantadine, levetiracetam, piracetam, clonazepam, propranolol, vitamin B6, and Ginkgo biloba. Other options, such as botulinum toxin and deep brain stimulation, will also be discussed, and a suggested treatment algorithm is provided. While these agents are reasonable treatment options at this time there is a need, with a concerted effort between neurology and psychiatry, for full-scale drug development, including multicenter, randomized, blinded trials to confirm the effectiveness of the agents that were positive in phase 2 trials and the development of newer ones.

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Acknowledgments

This work was supported by the Vance Lanier Endowed Chair in Neurology. The funding source had no input into the contents of this article. We would like to thank Thomas Wichmann, MD for his editorial advice. Full conflict of interest disclosures are available in the electronic supplementary material for this article.

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Dr. Factor has the following disclosures: honoraria—Scientiae for CME program, University of Florida speaker program, Current Neurology and Neuroscience section editor, Merz, Chelsea Therapeutics, ADAMAS; grants —Ceregene, TEVA, Ipsen, Allergan, Medtronics, Michael J. Fox Foundation, NIH; royalties—Demos, Blackwell Futura for textbooks. Dr. Zutshi had travel paid by UCB.

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Authors and Affiliations

  1. Department of Neurology, Emory University, 1841 Clifton Road NE, Atlanta, GA, 30329, USA

    Leslie J. Cloud, Deepti Zutshi & Stewart A. Factor

  2. Department of Neurology, Virginia Commonwealth University, 6605 W. Broad Street, Richmond, VA, USA

    Leslie J. Cloud

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  1. Leslie J. Cloud
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  2. Deepti Zutshi
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  3. Stewart A. Factor
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Correspondence to Stewart A. Factor.

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Cloud, L.J., Zutshi, D. & Factor, S.A. Tardive Dyskinesia: Therapeutic Options for an Increasingly Common Disorder. Neurotherapeutics 11, 166–176 (2014). https://doi.org/10.1007/s13311-013-0222-5

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