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Forgotten but not gone: new developments in the understanding and treatment of tardive dyskinesia

Published online by Cambridge University Press:  03 January 2017

Jonathan M. Meyer
Jonathan M. Meyer*
Affiliation:
Department of Psyshiatry, University of California, San Diego, California, USA California Department of State Hospitals (DSH), Psychopharmacology Resource Network, Patton, California, USA
*
*Address for correspondence: Jonathan M. Meyer, M.D., UCSD Dept. of Psychiatry, 4225 Executive Square, Suite 1130, La Jolla, CA 92037, USA. (Email: [email protected])
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Abstract

The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data. Using new insights into the metabolism of tetrabenazine and the properties of its active metabolites, 2 modifications of tetrabenazine have been synthesized to improve the kinetic profile, and are currently involved in double-blind placebo controlled studies aimed at U.S. Food and Drug Administration (FDA) regulatory approval. The possible availability of these new agents, deuterated tetrabenazine and valbenazine, significantly widens the range of treatment choices for patients with TD. For clinicians with patients at risk for TD due to dopamine antagonist exposure, experience has shown that the problem of TD will be an ongoing issue in modern psychiatry, and that an appreciation of new developments in the pathophysiology of, risk factors for, and treatment of TD is crucial to managing this condition.

Keywords

Amantadineantipsychoticgingkotardive dyskinesiatetrabenazine
Type
CME Review Article
Information
CNS Spectrums , Volume 21 , Supplement S1: CME SUPPLEMENT , December 2016 , pp. 13 - 24
Copyright
© Cambridge University Press 2016 

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Footnotes

This activity is supported by an unrestricted educational grant from Neurocrine Continental, Inc.

References

1. Vijayakumar, D, Jankovic, J. Drug-induced dyskinesia, part 1: treatment of levodopa-induced dyskinesia. Drugs. 2016; 76(7): 759–777.CrossRefGoogle ScholarPubMed
2. Vijayakumar, D, Jankovic, J. Drug-induced dyskinesia, part 2: treatment of tardive dyskinesia. Drugs. 2016; 76(7): 779–787.CrossRefGoogle ScholarPubMed
3. Merrill, RM, Lyon, JL, Matiaco, PM. Tardive and spontaneous dyskinesia incidence in the general population. BMC Psychiatry. 2013; 13(1): 152–160.CrossRefGoogle ScholarPubMed
4. Fenton, WS. Prevalence of spontaneous dyskinesia in schizophrenia. J Clin Psychiatry. 2000; 61(Suppl 4): 10–14.Google ScholarPubMed
5. Koning, JPF, Tenback, DE, van Os, J, Aleman, A, Kahn, RS, van Harten, PN. Dyskinesia and parkinsonism in antipsychotic-naive patients with schizophrenia, first-degree relatives and healthy controls: a meta-analysis. Schizophr Bull. 2010; 36(4): 723–731.CrossRefGoogle ScholarPubMed
6. Cloud, LJ, Zutshi, D, Factor, SA. Tardive dyskinesia: therapeutic options for an increasingly common disorder. Neurotherapeutics. 2014; 11(1): 166–176.CrossRefGoogle ScholarPubMed
7. Ryu, S, Yoo, JH, Kim, JH, et al. Tardive dyskinesia and tardive dystonia with second-generation antipsychotics in non-elderly schizophrenic patients unexposed to first-generation antipsychotics: a cross-sectional and retrospective study. J Clin Psychopharmacol. 2015; 35(1): 13–21.CrossRefGoogle ScholarPubMed
8. Kinon, BJ, Kollack-Walker, S, Jeste, D, et al. Incidence of tardive dyskinesia in older adult patients treated with olanzapine or conventional antipsychotics. J Geriatr Psychiatry Neurol. 2015; 28(1): 67–79.CrossRefGoogle ScholarPubMed
9. Teo, JT, Edwards, MJ, Bhatia, K. Tardive dyskinesia is caused by maladaptive synaptic plasticity: a hypothesis. Mov Disord. 2012; 27(10): 1205–1215.CrossRefGoogle ScholarPubMed
10. Rana, AQ, Chaudry, ZM, Blanchet, PJ. New and emerging treatments for symptomatic tardive dyskinesia. Drug Des Devel Ther. 2013; 7(6): 1329–1340.CrossRefGoogle ScholarPubMed
11. Aquino, CC, Lang, AE. Tardive dyskinesia syndromes: current concepts. Parkinsonism Relat Disord. 2014; 20(Suppl 1): S113–S117.CrossRefGoogle ScholarPubMed
12. Casey, DE. Tardive dyskinesia: pathophysiology and animal models. J Clin Psychiatry. 2000; 61(Suppl 4): 5–9.Google ScholarPubMed
13. Mahmoudi, S, Levesque, D, Blanchet, PJ. Upregulation of dopamine D3, not D2, receptors correlates with tardive dyskinesia in a primate model. Mov Disord. 2014; 29(9): 1125–1133.CrossRefGoogle ScholarPubMed
14. Segman, RH, Goltser, T, Heresco-Levy, U, et al. Association of dopaminergic and serotonergic genes with tardive dyskinesia in patients with chronic schizophrenia. Pharmacogenomics J. 2003; 3(5): 277–283.CrossRefGoogle ScholarPubMed
15. Le Foll, B, Wilson, AA, Graff, A, Boileau, I, Di Ciano, P. Recent methods for measuring dopamine D3 receptor occupancy in vivo: importance for drug development. Front Pharmacol. 2014; 5(1): 161.CrossRefGoogle ScholarPubMed
16. Son, WY, Lee, HJ, Yoon, HK, et al. Gaba transporter SLC6A11 gene polymorphism associated with tardive dyskinesia. Nord J Psychiatry. 2014; 68(2): 123–128.CrossRefGoogle ScholarPubMed
17. Inada, T, Koga, M, Ishiguro, H, et al. Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia. Pharmacogenet Genomics. 2008; 18(4): 317–323.CrossRefGoogle ScholarPubMed
18. Zai, CC, Tiwari, AK, Mazzoco, M, et al. Association study of the vesicular monoamine transporter gene SLC18A2 with tardive dyskinesia. J Psychiatr Res. 2013; 47(11): 1760–1765.CrossRefGoogle ScholarPubMed
19. Lohr, JB, Browning, JA. Free radical involvement in neuropsychiatric illnesses. Psychopharmacol Bull. 1995; 31(1): 159–165.Google ScholarPubMed
20. Lohr, JB, Kuczenski, R, Niculescu, AB. Oxidative mechanisms and tardive dyskinesia. CNS Drugs. 2003; 17(1): 47–62.CrossRefGoogle ScholarPubMed
21. Cho, CH, Lee, HJ. Oxidative stress and tardive dyskinesia: pharmacogenetic evidence. Prog Neuropsychopharmacol Biol Psychiatry. 2013; 46(1): 207–213.CrossRefGoogle ScholarPubMed
22. An, HM, Tan, YL, Shi, J, et al. Altered IL-2, IL-6 and IL-8 serum levels in schizophrenia patients with tardive dyskinesia. Schizophr Res. 2015; 162(1–3): 261–268.CrossRefGoogle ScholarPubMed
23. Grover, S, Kumar, P, Singh, K, Vikram, V, Budhiraja, RD. Possible beneficial effect of peroxisome proliferator-activated receptor (PPAR)—alpha and gamma agonist against a rat model of oral dyskinesia. Pharmacol Biochem Behav. 2013; 111(1): 17–23.CrossRefGoogle ScholarPubMed
24. Richardson, MA, Small, AM, Read, LL, Chao, HM, Clelland, JD. Branched chain amino acid treatment of tardive dyskinesia in children and adolescents. J Clin Psychiatry. 2004; 65(1): 92–96.CrossRefGoogle ScholarPubMed
25. Pouclet-Courtemanche, H, Rouaud, T, Thobois, S, et al. Long-term efficacy and tolerability of bilateral pallidal stimulation to treat tardive dyskinesia. Neurology. 2016; 86(7): 651–659.CrossRefGoogle ScholarPubMed
26. Sarró, S, Pomarol-Clotet, E, Canales-Rodríguez, EJ, et al. Structural brain changes associated with tardive dyskinesia in schizophrenia. Br J Psychiatry. 2013; 203(1): 51–57.CrossRefGoogle ScholarPubMed
27. Zhang, XY, Xiu, MH, Chen da, C, et al. Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. J Psychiatr Res. 2010; 44(7): 429–433.CrossRefGoogle ScholarPubMed
28. Bhidayasiri, R, Fahn, S, Weiner, WJ, et al. Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013; 81(5): 463–469.CrossRefGoogle Scholar
29. Soares, KV, McGrath, JJ. Vitamin E for neuroleptic-induced tardive dyskinesia. Cochrane Database Syst Rev. 2001;(4): CD000209.Google ScholarPubMed
30. Thaker, GK, Nguyen, JA, Strauss, ME, Jacobson, R, Kaup, BA, Tamminga, CA. Clonazepam treatment of tardive dyskinesia: a practical GABAmimetic strategy. Am J Psychiatry. 1990; 147(4): 445–451.Google ScholarPubMed
31. Angus, S, Sugars, J, Boltezar, R, Koskewich, S, Schneider, NM. A controlled trial of amantadine hydrochloride and neuroleptics in the treatment of tardive dyskinesia. J Clin Psychopharmacol. 1997; 17(2): 88–91.CrossRefGoogle ScholarPubMed
32. Pappa, S, Tsouli, S, Apostolou, G, Mavreas, V, Konitsiotis, S. Effects of amantadine on tardive dyskinesia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2010; 33(6): 271–275.CrossRefGoogle ScholarPubMed
33. Zhang, WF, Tan, YL, Zhang, XY, Chan, RC, Wu, HR, Zhou, DF. Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011; 72(5): 615–621.CrossRefGoogle ScholarPubMed
34. Chandler, JH. Reserpine in the treatment of Huntington’s chorea. Med Bull (Ann Arbor). 1955; 21(4): 95–100.Google ScholarPubMed
35. Lazarte, JA, Petersen, MC, Baars, CW, et al. Huntington’s chorea: results of treatment with reserpine. Proc Staff Meet Mayo Clin. 1955; 30(16): 358–365.Google ScholarPubMed
36. Quinn, GP, Shore, PA, Brodie, BB. Biochemical and pharmacological studies of RO 1-9569 (tetrabenazine), a nonindole tranquilizing agent with reserpine-like effects. J Pharmacol Exp Ther. 1959; 127: 103–109.Google ScholarPubMed
37. Kazamatsuri, H, Chien, C, Cole, JO. Treatment of tardive dyskinesia. I. Clinical efficacy of a dopamine-depleting agent, tetrabenazine. Arch Gen Psychiatry. 1972; 27(1): 95–99.CrossRefGoogle ScholarPubMed
38. Scherman, D, Weber, MJ. Characterization of the vesicular monoamine transporter in cultured rat sympathetic neurons: persistence upon induction of cholinergic phenotypic traits. Dev Biol. 1987; 119(1): 68–74.CrossRefGoogle ScholarPubMed
39. Roghani, A, Feldman, J, Kohan, SA, et al. Molecular cloning of a putative vesicular transporter for acetylcholine. Proc Natl Acad Sci U S A. 1994; 91(22): 10620–10624.CrossRefGoogle ScholarPubMed
40. Erickson, JD, Eiden, LE, Schafer, MK, Weihe, E. Reserpine- and tetrabenazine-sensitive transport of (3)H-histamine by the neuronal isoform of the vesicular monoamine transporter. J Mol Neurosci. 1995; 6(4): 277–287.CrossRefGoogle ScholarPubMed
41. Erickson, JD, Schafer, MK, Bonner, TI, Eiden, LE, Weihe, E. Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1996; 93(10): 5166–5171.CrossRefGoogle ScholarPubMed
42. Kilbourn, M, Lee, L, Vander Borght, T, Jewett, D, Frey, K. Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific. Eur J Pharmacol. 1995; 278(3): 249–252.CrossRefGoogle Scholar
43. Kilbourn, MR, Lee, LC, Heeg, MJ, Jewett, DM. Absolute configuration of (+)-alpha-dihydrotetrabenazine, an active metabolite of tetrabenazine. Chirality. 1997; 9(1): 59–62.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
44. Mehanna, R, Hunter, C, Davidson, A, Jimenez-Shahed, J, Jankovic, J. Analysis of CYP2D6 genotype and response to tetrabenazine. Mov Disord. 2013; 28(2): 210–215.CrossRefGoogle ScholarPubMed
45. Muller, T. Valbenazine granted breakthrough drug status for treating tardive dyskinesia. Expert Opin Investig Drugs. 2015; 24(6): 737–742.CrossRefGoogle ScholarPubMed
46. Jankovic, J, Clarence-Smith, K. Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders. Expert Rev Neurother. 2011; 11(11): 1509–1523.CrossRefGoogle ScholarPubMed
47. SEC Form S-1 Registration Statement of Auspex Pharmaceuticals, Inc. December 20, 2013. https://www.sec.gov/Archives/edgar/data/1454189/000119312513481239/d627086ds1.htm. Accessed 7/1/2016.Google Scholar
48. Huntington Study Group, Frank, S, Testa, CM, Stamler, D, et al. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA. 2016; 316(1): 40–50.Google ScholarPubMed
49. Anderson, KE, Factor, SA, Hauser, RA, et al. A randomized, double-blind, placebo-controlled trial of deutetrabenazine for the treatment of tardive dyskinesia (ARM-TD). Poster presented at: The American Psychiatric Association Annual Meeting; May 14–18, 2016; Atlanta, GA.Google Scholar
50. Yao, Z, Wei, X, Wu, X, et al. Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors. Eur J Med Chem. 2011; 46(5): 1841–1848.CrossRefGoogle ScholarPubMed
51. O’Brien, CF, Jimenez, R, Hauser, RA, et al. NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: a randomized, double-blind, placebo-controlled study. Mov Disord. 2015; 30(12): 1681–1687.CrossRefGoogle ScholarPubMed
52. Josiassen, RC, Remington, G, Burke, J, et al. Valbenazine (NBI-98854) is effective for treating tardive dyskinesia in individuals with schizophrenia or mood disorder. Poster presented at: The American Psychiatric Association Annual Meeting; May 14–18, 2016; Atlanta, GA.Google Scholar
53. Marder, S, Knesevich, MA, Hauser, RA, et al. KINECT 3: a randomized, double-blind, placebo-controlled phase 3 trial of valbenazine (NBI-98854) for tardive dyskinesia. Poster presented at: The American Psychiatric Association Annual Meeting; May 14–18, 2016; Atlanta, GA.Google Scholar
54. Leung, JG, Breden, EL. Tetrabenazine for the treatment of tardive dyskinesia. Ann Pharmacother. 2011; 45(4): 525–531.CrossRefGoogle ScholarPubMed