, Volume 78, Issue 5, pp 525–541 | Cite as

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

  • Nicki Niemann
  • Joseph JankovicEmail author
Therapy in Practice


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.


Author contributions

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.


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

Compliance with Ethical Standards

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.


  1. 1.
    Faurbye A, Rasch PJ, Petersen PB, Brandborg G, Pakkenberg H. Neurological symptoms in pharmacotherapy of psychoses. Acta Psychiatr Scand. 1964;40:10–27.PubMedCrossRefGoogle Scholar
  2. 2.
    Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinetic Mov. 2013;3:1–11.Google Scholar
  3. 3.
    Vijayakumar D, Jankovic J. Drug-induced dyskinesia, part 2: Treatment of tardive dyskinesia. Drugs. 2016;76:779–87.PubMedCrossRefGoogle Scholar
  4. 4.
    Savitt D, Jankovic J. Tardive syndromes. J Neurol Sci. 2018 (in press).Google Scholar
  5. 5.
    Frei K, Truong DD, Fahn S, Jankovic J, Hauser RA. The nosology of tardive syndromes. J Neurol Sci. 2018. Scholar
  6. 6.
    Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78:e264–78.PubMedCrossRefGoogle Scholar
  7. 7.
    Correll CU, Kane JM, Citrome LL. Epidemiology, prevention, and assessment of tardive dyskinesia and advances in treatment. J Clin Psychiatry. 2017;78:1136–47.PubMedCrossRefGoogle Scholar
  8. 8.
    Pillay J, Boylan K, Carrey N, Newton A, Vandermeer B, Nuspl M, et al. First- and second-generation antipsychotics in children and young adults: Systematic review update [Internet]. Agency for Healthcare Research and Quality (US); 2017 [cited 2018 Jan 20]. Available from:
  9. 9.
    McDonagh M, Peterson K, Carson S, Fu R, Thakurta S. Drug class review: Atypical antipsychotic drugs: final update 3 report [Internet]. Portland (OR): Oregon Health & Science University; 2010. Available from:
  10. 10.
    Kwei K, Frucht S. Acute presentation of nonmotor symptoms in parkinson’s disease. Int Rev Neurobiol. 2017;134:973–86.PubMedCrossRefGoogle Scholar
  11. 11.
    Patel N, Jankovic J, Hallett M. Sensory aspects of movement disorders. Lancet Neurol. 2014;13:100–12.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Caroff SN, Campbell EC. Drug-induced extrapyramidal syndromes: implications for contemporary practice. Psychiatr Clin North Am. 2016;39:391–411.PubMedCrossRefGoogle Scholar
  13. 13.
    Obeso JA. The movement disorders journal 2016 and onward. Mov Disord. 2016;31:1–2.PubMedCrossRefGoogle Scholar
  14. 14.
    Walker RH. Thoughts on selected movement disorder terminology and a plea for clarity. Tremor Other Hyperkinet Mov (N Y). 2013;3.
  15. 15.
    Medication-induced movement disorders and other adverse effects of medication. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013. p. 709–14.Google Scholar
  16. 16.
    Emsley R, Niehaus DJH, Oosthuizen PP, Koen L, Chiliza B, Fincham D. Subjective awareness of tardive dyskinesia and insight in schizophrenia. Eur Psychiatry. 2011;26:293–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Cloud LJ, Zutshi D, Factor SA. Tardive dyskinesia: therapeutic options for an increasingly common disorder. Neurotherapeutics. 2014;11:166–76.PubMedCrossRefGoogle Scholar
  18. 18.
    Mehta SH, Morgan JC, Sethi KD. Drug-induced movement disorders. Neurol Clin. 2015;33:153–74.PubMedCrossRefGoogle Scholar
  19. 19.
    Lorberboym M, Treves TA, Melamed E, Lampl Y, Hellmann M, Djaldetti R. [123I]-FP/CIT SPECT imaging for distinguishing drug-induced parkinsonism from Parkinson’s disease. Mov Disord. 2006;21:510–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Lo Y-C, Peng Y-C. Amisulpride withdrawal dyskinesia: a case report. Ann Gen Psychiatry. 2017;16:25.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Blanchet PJ, Popovici R, Guitard F, Rompré PH, Lamarche C, Lavigne GJ. Pain and denture condition in edentulous orodyskinesia: comparisons with tardive dyskinesia and control subjects. Mov Disord. 2008;23:1837–42.PubMedCrossRefGoogle Scholar
  22. 22.
    Shin H-Y, Yoon WT, Lee WY. Anticholinergic agents can induce oromandibular dyskinesia. J Mov Disord. 2009;2:69–71.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Vijayakumar D, Jankovic J. Drug-induced dyskinesia, part 1: treatment of levodopa-induced dyskinesia. Drugs. 2016;76:759–77.PubMedCrossRefGoogle Scholar
  24. 24.
    Fekete R, Jankovic J. Upper facial chorea in Huntington disease. J Clin Mov Disord. 2014;1:7.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Cardoso F. Differential diagnosis of Huntington’s disease: what the clinician should know. Neurodegener Dis Manag. 2014;4:67–72.PubMedCrossRefGoogle Scholar
  26. 26.
    Singer HS, Mink JW, Gilbert DL, Jankovic J. Inherited metabolic disorders with associated movement abnormalities. In: Movement disorders in childhood. 2nd ed. London: Academic Press; 2016. p. 337–407.Google Scholar
  27. 27.
    Thenganatt MA, Jankovic J. Recent advances in understanding and managing Tourette syndrome [version 1; referees: 3 approved]. F1000Research 2016, 5(F1000 Faculty Rev):152.
  28. 28.
    Baizabal-Carvallo JF, Jankovic J. Movement disorders in autoimmune diseases. Mov Disord. 2012;27:935–46.PubMedCrossRefGoogle Scholar
  29. 29.
    Benazzi F. Rapid onset of tardive dyskinesia in Huntington disease with olanzapine. J Clin Psychopharmacol. 2002;22:438–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Singh SK, Jankovic J. Tardive dystonia in patients with Tourette’s syndrome. Mov Disord. 1988;3:274–80.PubMedCrossRefGoogle Scholar
  31. 31.
    Kane JM, Woerner M, Lieberman J. Tardive dyskinesia: prevalence, incidence, and risk factors. J Clin Psychopharmacol. 1988;8:52S–6S.PubMedCrossRefGoogle Scholar
  32. 32.
    Yassa R, Jeste DV. Gender differences in tardive dyskinesia: a critical review of the literature. Schizophr Bull. 1992;18:701–15.PubMedCrossRefGoogle Scholar
  33. 33.
    Gardos G, Casey DE, Cole JO, Perenyi A, Kocsis E, Arato M, et al. Ten-year outcome of tardive dyskinesia. Am J Psychiatry. 1994;151:836–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Glazer WM, Morgenstern H, Doucette JT. Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications. J Clin Psychiatry. 1993;54:133–9.PubMedGoogle Scholar
  35. 35.
    Chakos MH, Alvir JM, Woerner MG, Koreen A, Geisler S, Mayerhoff D, et al. Incidence and correlates of tardive dyskinesia in first episode of schizophrenia. Arch Gen Psychiatry. 1996;53:313–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Jeste DV, Caligiuri MP, Paulsen JS, Heaton RK, Lacro JP, Harris MJ, et al. Risk of tardive dyskinesia in older patients. A prospective longitudinal study of 266 outpatients. Arch Gen Psychiatry. 1995;52:756–65.PubMedCrossRefGoogle Scholar
  37. 37.
    Woerner MG, Alvir JMJ, Saltz BL, Lieberman JA, Kane JM. Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry. 1998;155:1521–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Correll CU, Leucht S, Kane JM. Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. Am J Psychiatry. 2004;161:414–25.PubMedCrossRefGoogle Scholar
  39. 39.
    O’Brien A. Comparing the risk of tardive dyskinesia in older adults with first-generation and second-generation antipsychotics: a systematic review and meta-analysis. Int J Geriatr Psychiatry. 2016;31:683–93.PubMedCrossRefGoogle Scholar
  40. 40.
    Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382:951–62.PubMedCrossRefGoogle Scholar
  41. 41.
    Arnt J, Skarsfeldt T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998;18:63–101.PubMedCrossRefGoogle Scholar
  42. 42.
    Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry. 2008;21:151–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Miller DD, Caroff SN, Davis SM, Rosenheck RA, McEvoy JP, Saltz BL, et al. Extrapyramidal side-effects of antipsychotics in a randomised trial. Br J Psychiatry. 2008;193:279–88.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Peluso MJ, Lewis SW, Barnes TRE, Jones PB. Extrapyramidal motor side-effects of first- and second-generation antipsychotic drugs. Br J Psychiatry. 2012;200:387–92.PubMedCrossRefGoogle Scholar
  45. 45.
    Hazari N, Kate N, Grover S. Clozapine and tardive movement disorders: a review. Asian J Psychiatr. 2013;6:439–51.PubMedCrossRefGoogle Scholar
  46. 46.
    Li C-R, Chung Y-C, Park T-W, Yang J-C, Kim K-W, Lee K-H, et al. Clozapine-induced tardive dyskinesia in schizophrenic patients taking clozapine as a first-line antipsychotic drug. World J Biol Psychiatry. 2009;10:919–24.PubMedCrossRefGoogle Scholar
  47. 47.
    Davé M. Clozapine-related tardive dyskinesia. Biol Psychiatry. 1994;35:886–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Molho ES, Factor SA. Possible tardive dystonia resulting from clozapine therapy. Mov Disord. 1999;14:873–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Peña MS, Yaltho TC, Jankovic J. Tardive dyskinesia and other movement disorders secondary to aripiprazole. Mov Disord. 2011;26:147–52.PubMedCrossRefGoogle Scholar
  50. 50.
    Paulson GW, Rizvi CA, Crane GE. Tardive dyskinesia as a possible sequel of long-term therapy with phenothiazines. Clin Pediatr (Phila). 1975;14:953–5.Google Scholar
  51. 51.
    Campbell M, Armenteros JL, Malone RP, Adams PB, Eisenberg ZW, Overall JE. Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. J Am Acad Child Adolesc Psychiatry. 1997;36:835–43.PubMedCrossRefGoogle Scholar
  52. 52.
    McAndrew JB, Case Q, Treffert DA. Effects of prolonged phenothiazine intake on psychotic and other hospitalized children. J Autism Child Schizophr. 1972;2:75–91.PubMedCrossRefGoogle Scholar
  53. 53.
    Mejia NI, Jankovic J. Tardive dyskinesia and withdrawal emergent syndrome in children. Expert Rev Neurother. 2010;10:893–901.PubMedCrossRefGoogle Scholar
  54. 54.
    Wonodi I, Reeves G, Carmichael D, Verovsky I, Avila MT, Elliott A, et al. Tardive dyskinesia in children treated with atypical antipsychotic medications. Mov Disord. 2007;22:1777–82.PubMedCrossRefGoogle Scholar
  55. 55.
    Garcia-Amador M, Merchán-Naranjo J, Tapia C, Moreno C, Castro-Fornieles J, Baeza I, et al. Neurological adverse effects of antipsychotics in children and adolescents. J Clin Psychopharmacol. 2015;35:686–93.PubMedCrossRefGoogle Scholar
  56. 56.
    Hugenholtz GWK, Heerdink ER, Stolker JJ, Meijer WEE, Egberts ACG, Nolen WA. Haloperidol dose when used as active comparator in randomized controlled trials with atypical antipsychotics in schizophrenia: comparison with officially recommended doses. J Clin Psychiatry. 2006;67:897–903.PubMedCrossRefGoogle Scholar
  57. 57.
    Rakesh G, Muzyk A, Szabo ST, Gupta S, Pae C-U, Masand P. Tardive dyskinesia: 21st century may bring new treatments to a forgotten disorder. Ann Clin Psychiatry. 2017;29:108–19.PubMedGoogle Scholar
  58. 58.
    Achalia RM, Chaturvedi SK, Desai G, Rao GN, Prakash O. Prevalence and risk factors associated with tardive dyskinesia among Indian patients with schizophrenia. Asian J Psychiatr. 2014;9:31–5.PubMedCrossRefGoogle Scholar
  59. 59.
    van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS. Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curaçao Extrapyramidal Syndromes Study III. Am J Psychiatry. 1998;155:565–7.PubMedCrossRefGoogle Scholar
  60. 60.
    Xiang Y-T, Wang C-Y, Si T-M, Lee EHM, He Y-L, Ungvari GS, et al. Sex differences in use of psychotropic drugs and drug-induced side effects in schizophrenia patients: findings of the research on Asia psychotropic prescription (REAP) studies. Aust N Zeal J Psychiatry. 2011;45:193–8.CrossRefGoogle Scholar
  61. 61.
    Zhang XY, Chen DC, Qi LY, Wang F, Xiu MH, Chen S, et al. Gender differences in the prevalence, risk and clinical correlates of tardive dyskinesia in Chinese schizophrenia. Psychopharmacology. 2009;205:647–54.PubMedCrossRefGoogle Scholar
  62. 62.
    Tenback DE, van Harten PN, van Os J. Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis. Mov Disord. 2009;24:2309–15.PubMedCrossRefGoogle Scholar
  63. 63.
    Wijemanne S, Jankovic J, Evans RW. Movement disorders from the use of metoclopramide and other antiemetics in the treatment of migraine. Headache J Head Face Pain. 2016;56:153–61.CrossRefGoogle Scholar
  64. 64.
    Kenney C, Hunter C, Davidson A, Jankovic J. Metoclopramide, an increasingly recognized cause of tardive dyskinesia. J Clin Pharmacol. 2008;48:379–84.PubMedCrossRefGoogle Scholar
  65. 65.
    Pasricha PJ, Pehlivanov N, Sugumar A, Jankovic J. Drug Insight: from disturbed motility to disordered movement—a review of the clinical benefits and medicolegal risks of metoclopramide. Nat Clin Pract Gastroenterol Hepatol. 2006;3:138–48.PubMedCrossRefGoogle Scholar
  66. 66.
    Mejia NI, Jankovic J. Metoclopramide-induced tardive dyskinesia in an infant. Mov Disord. 2005;20:86–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Loonen AJM, Ivanova SA. New insights into the mechanism of drug-induced dyskinesia. CNS Spectr. 2013;18:15–20.PubMedCrossRefGoogle Scholar
  68. 68.
    Stahl SM. Neuronal traffic signals in tardive dyskinesia: not enough “stop” in the motor striatum. CNS Spectr. 2017;22:427–34.PubMedCrossRefGoogle Scholar
  69. 69.
    Turrone P, Remington G, Kapur S, Nobrega JN. The relationship between dopamine D2 receptor occupancy and the vacuous chewing movement syndrome in rats. Psychopharmacology. 2003;165:166–71.PubMedCrossRefGoogle Scholar
  70. 70.
    Silvestri S, Seeman MV, Negrete JC, Houle S, Shammi CM, Remington GJ, et al. Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology. 2000;152:174–80.PubMedCrossRefGoogle Scholar
  71. 71.
    Strange PG. Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol Rev. 2001;53:119–33.PubMedGoogle Scholar
  72. 72.
    Seeman P. Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010;4:56–73.PubMedCrossRefGoogle Scholar
  73. 73.
    Shi J, Tan YL, Wang ZR, An HM, Li J, Wang YC, et al. Ginkgo biloba and vitamin E ameliorate haloperidol-induced vacuous chewingmovement and brain-derived neurotrophic factor expression in a rat tardive dyskinesia model. Pharmacol Biochem Behav. 2016;148:53–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Teo JT, Edwards MJ, Bhatia K. Tardive dyskinesia is caused by maladaptive synaptic plasticity: a hypothesis. Mov Disord. 2012;27:1205–15.PubMedCrossRefGoogle Scholar
  75. 75.
    Lanning RK, Zai CC, Müller DJ. Pharmacogenetics of tardive dyskinesia: an updated review of the literature. Pharmacogenomics. 2016;17:1339–51.PubMedCrossRefGoogle Scholar
  76. 76.
    Guy W. AIMS: ECDEU assessment manual for psychopharmacology. Washington, DC: Government Printing Office; 1976. p. 534–7.Google Scholar
  77. 77.
    Munetz MR, Benjamin S. How to examine patients using the Abnormal Involuntary Movement Scale. Hosp Community Psychiatry. 1988;39:1172–7.PubMedGoogle Scholar
  78. 78.
    Bark N, Florida D, Gera N, Varardi R, Harghel L, Adlington K. Evaluation of the routine clinical use of the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). J Psychiatr Pract. 2011;17:300–3.PubMedCrossRefGoogle Scholar
  79. 79.
    Suzuki T. Which rating scales are regarded as “the standard” in clinical trials for schizophrenia? A critical review. Psychopharmacol Bull. 2011;44:18–31.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Lane RD, Glazer WM, Hansen TE, Berman WH, Kramer SI. Assessment of tardive dyskinesia using the Abnormal Involuntary Movement Scale. J Nerv Ment Dis. 1985;173:353–7.PubMedCrossRefGoogle Scholar
  81. 81.
    Gerlach J, Korsgaard S, Clemmesen P, Lauersen AM, Magelund G, Noring U, et al. The St. Hans Rating Scale for extrapyramidal syndromes: reliability and validity. Acta Psychiatr Scand. 1993;87:244–52.PubMedCrossRefGoogle Scholar
  82. 82.
    Domino ME, Swartz MS. Who are the new users of antipsychotic medications? Psychiatr Serv. 2008;59:507–14.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Huskamp HA, Horvitz-Lennon M, Berndt ER, Normand S-LT, Donohue JM. Patterns of antipsychotic prescribing by physicians to young children. Psychiatr Serv. 2016;67:1307–14.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Hálfdánarson Ó, Zoëga H, Aagaard L, Bernardo M, Brandt L, Fusté AC, et al. International trends in antipsychotic use: a study in 16 countries, 2005–2014. Eur Neuropsychopharmacol. 2017;27:1064–76.PubMedCrossRefGoogle Scholar
  85. 85.
    Seeberger LC, Hauser RA. Valbenazine for the treatment of tardive dyskinesia. Expert Opin Pharmacother. 2017;18:1279–87.PubMedCrossRefGoogle Scholar
  86. 86.
    Ehrenpreis ED, Deepak P, Sifuentes H, Devi R, Du H, Leikin JB. The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits. Am J Gastroenterol. 2013;108:866–72.PubMedCrossRefGoogle Scholar
  87. 87.
    Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161:1–56.Google Scholar
  88. 88.
    Viguera AC, Baldessarini RJ, Hegarty JD, van Kammen DP, Tohen M. Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Arch Gen Psychiatry. 1997;54:49–55.PubMedCrossRefGoogle Scholar
  89. 89.
    Bhidayasiri R, Fahn S, Weiner WJ, Gronseth GS, Sullivan KL, Zesiewicz TA, et al. Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;81:463–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Sahli ZT, Tarazi FI. Pimavanserin: novel pharmacotherapy for Parkinson’s disease psychosis. Expert Opin Drug Discov. 2018;13:103–10.PubMedCrossRefGoogle Scholar
  91. 91.
    Glazer WM, Morgenstern H, Schooler N, Berkman CS, Moore DC. Predictors of improvement in tardive dyskinesia following discontinuation of neuroleptic medication. Br J Psychiatry. 1990;157:585–92.PubMedCrossRefGoogle Scholar
  92. 92.
    Zutshi D, Cloud LJ, Factor SA. Tardive syndromes are rarely reversible after discontinuing dopamine receptor blocking agents: experience from a university-based movement disorder clinic. Tremor Other Hyperkinetic Mov (N Y). 2014;4:266.PubMedCentralGoogle Scholar
  93. 93.
    Modestin J, Wehrli MV, Stephan PL, Agarwalla P. Evolution of neuroleptic-induced extrapyramidal syndromes under long-term neuroleptic treatment. Schizophr Res. 2008;100:97–107.PubMedCrossRefGoogle Scholar
  94. 94.
    Fernandez HH, Krupp B, Friedman JH. The course of tardive dyskinesia and parkinsonism in psychiatric inpatients: 14-year follow-up. Neurology. 2001;56:805–7.PubMedCrossRefGoogle Scholar
  95. 95.
    Bhidayasiri R, Jitkritsadakul O, Friedman JH, Fahn S. Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm. J Neurol Sci. 2018. Scholar
  96. 96.
    Lawal HO, Krantz DE. SLC18: vesicular neurotransmitter transporters for monoamines and acetylcholine. Mol Aspects Med. 2013;34:360–72.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Jankovic J. Progress in Parkinson disease and other movement disorders. Nat Rev Neurol. 2017;13:76–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Benarroch EE. Monoamine transporters: structure, regulation, and clinical implications. Neurology. 2013;81:761–8.PubMedCrossRefGoogle Scholar
  99. 99.
    Jankovic J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opin Pharmacother. 2016;17:2461–70.PubMedCrossRefGoogle Scholar
  100. 100.
    LeWitt PA. Tardive dyskinesia caused by tetrabenazine. Clin Neuropharmacol. 2013;36:92–3.PubMedCrossRefGoogle Scholar
  101. 101.
    Caroff SN, Davis VG, Miller DD, Davis SM, Rosenheck RA, McEvoy JP, et al. Treatment outcomes of patients with tardive dyskinesia and chronic schizophrenia. J Clin Psychiatry. 2011;72:295–303.PubMedCrossRefGoogle Scholar
  102. 102.
    Stahl SM. Mechanism of action of vesicular monoamine transporter 2 (VMAT2) inhibitors in tardive dyskinesia: reducing dopamine leads to less “go” and more “stop” from the motor striatum for robust therapeutic effects. CNS Spectr. 2017;23:1–6.PubMedCrossRefGoogle Scholar
  103. 103.
    Lundbeck. Xenazine (tetrabenazine), Highlights of Prescribing Information. [cited 2018 Jan 4]; Available from:
  104. 104.
    Austedo (deutetrabenazine) Tablets, Medical Review(s). [cited 2018 Jan 4]; Available from:
  105. 105.
    Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic characterization of valbenazine (NBI-98854) and its metabolites. J Pharmacol Exp Ther. 2017;361:454–61.PubMedCrossRefGoogle Scholar
  106. 106.
    Mehanna R, Hunter C, Davidson A, Jimenez-Shahed J, Jankovic J. Analysis of CYP2D6 genotype and response to tetrabenazine. Mov Disord. 2013;28:210–5.PubMedCrossRefGoogle Scholar
  107. 107.
    Teva Pharmaceuticals. Austedo (deutetrabenazine), Highlights of Prescribing Information. [cited 2018 Jan 4]; Available from:
  108. 108.
    Neurocrine Biosciences. Ingrezza (valbenazine), Highlights of Prescribing Information. [cited 2018 Jan 4]; Available from:
  109. 109.
    Ondo WG, Hanna PA, Jankovic J. Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol. Am J Psychiatry. 1999;156:1279–81.PubMedGoogle Scholar
  110. 110.
    Kazamatsuri H, Chien C, Cole JO. Treatment of tardive dyskinesia. I. Clinical efficacy of a dopamine-depleting agent, tetrabenazine. Arch Gen Psychiatry. 1972;27:95–9.PubMedCrossRefGoogle Scholar
  111. 111.
    Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord. 2007;22:193–7.PubMedCrossRefGoogle Scholar
  112. 112.
    Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology. 1997;48:358–62.PubMedCrossRefGoogle Scholar
  113. 113.
    Kenney C, Hunter C, Mejia N, Jankovic J. Is history of depression a contraindication to treatment with tetrabenazine? Clin Neuropharmacol. 2006;29:259–64.PubMedCrossRefGoogle Scholar
  114. 114.
    Gant TG. Using deuterium in drug discovery: leaving the label in the drug. J Med Chem. 2014;57:3595–611.PubMedCrossRefGoogle Scholar
  115. 115.
    Stamler D, Bradbury M, Brown F. The pharmacokinetics and safety of deuterated-tetrabenazine. Neurology. 2013;80:P07.210.Google Scholar
  116. 116.
    Fernandez HH, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, et al. Randomized controlled trial of deutetrabenazine for tardive dyskinesia. Neurology. 2017;88:2003–10.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Anderson KE, Stamler D, Davis MD, Factor SA, Hauser RA, Isojärvi J, et al. Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Psychiatry. 2017;4:595–604.PubMedCrossRefGoogle Scholar
  118. 118.
    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. 2017;71:e13030.CrossRefGoogle Scholar
  119. 119. Reducing involuntary movements in tardive dyskinesia. NCT02198794. [Internet]. Auspex Pharm. Inc. 2017 [cited 2017 Nov 6]. Available from:
  120. 120.
    Anderson K, Stamler D, Davis M, Factor S, Hauser R, Isojärvi J, et al. Long-term safety of deutetrabenazine for the treatment of tardive dyskinesia: results from an open-label, long-term study [abstract]. Mov Disord. 2017;32 (suppl 2). [Internet]. [cited 2018 Jan 4]. Available from:
  121. 121.
    Frank S, Stamler D, Kayson E, Claassen DO, Colcher A, Davis C, et al. Safety of converting from tetrabenazine to deutetrabenazine for the treatment of chorea. JAMA Neurol. 2017;74:977–82.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Bashir H, Jankovic J. Treatment options for chorea. Expert Rev Neurother. 2018;18:51–63.PubMedCrossRefGoogle Scholar
  123. 123.
    Jankovic J, Jimenez-Shahed J, Budman C, Coffey B, Murphy T, Shprecher D, et al. Deutetrabenazine in tics associated with tourette syndrome. Tremor Other Hyperkinetic Mov (N Y). 2016;6:422.Google Scholar
  124. 124.
    Müller T. Valbenazine for the treatment of tardive dyskinesia. Expert Rev Neurother. 2017;17:1135–44.PubMedCrossRefGoogle Scholar
  125. 125.
    Caroff SN, Aggarwal S, Yonan C. Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review. J Comp Eff Res. 2017;6:422.Google Scholar
  126. 126.
    O’Brien CF, Jimenez R, Hauser RA, Factor SA, Burke J, Mandri D, 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;30:1681–7.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Hauser RA, Factor SA, Marder SR, Knesevich MA, Ramirez PM, Jimenez R, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174:476–84.PubMedCrossRefGoogle Scholar
  128. 128.
    Citrome L. Valbenazine 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. 2017;71:e12964.CrossRefGoogle Scholar
  129. 129.
    Thai-Cuarto D, O’Brien CF, Jimenez R, Liang GS, Burke J. Cardiovascular profile of valbenazine: analysis of pooled data from three randomized, double-blind, placebo-controlled trials. Drug Saf. 2017. Scholar
  130. 130.
    Factor SA, Remington G, Comella CL, Correll CU, Burke J, Jimenez R, et al. The effects of valbenazine in participants with tardive dyskinesia: results of the 1-year KINECT 3 extension study. J Clin Psychiatry. 2017;78:1344–50.PubMedCrossRefGoogle Scholar
  131. 131.
    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;17:88–91.PubMedCrossRefGoogle Scholar
  132. 132.
    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;33:271–5.PubMedCrossRefGoogle Scholar
  133. 133.
    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;147:445–51.PubMedCrossRefGoogle Scholar
  134. 134.
    Zheng W, Xiang Y-Q, Ng C, Ungvari G, Chiu H, Xiang Y-T. Extract of Ginkgo biloba for tardive dyskinesia: meta-analysis of randomized controlled trials. Pharmacopsychiatry. 2016;49:107–11.PubMedCrossRefGoogle Scholar
  135. 135.
    Zhang W-F, Tan Y-L, Zhang X-Y, Chan RCK, Wu H-R, Zhou D-F. Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011;72:615–21.PubMedCrossRefGoogle Scholar
  136. 136.
    Zhang XY, Zhang W-F, Zhou D-F, Chen DC, Xiu MH, Wu H-R, et al. Brain-derived neurotrophic factor levels and its Val66Met gene polymorphism predict tardive dyskinesia treatment response to Ginkgo biloba. Biol Psychiatry. 2012;72:700–6.PubMedCrossRefGoogle Scholar
  137. 137.
    Desmarais JE, Beauclair L, Annable L, Bélanger M-C, Kolivakis TT, Margolese HC. Effects of discontinuing anticholinergic treatment on movement disorders, cognition and psychopathology in patients with schizophrenia. Ther Adv Psychopharmacol. 2014;4:257–67.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Vinogradov S, Fisher M, Warm H, Holland C, Kirshner MA, Pollock BG. The cognitive cost of anticholinergic burden: Decreased response to cognitive training in schizophrenia. Am J Psychiatry. 2009;166:1055–62.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Aquino CCH, Lang AE. Tardive dyskinesia syndromes: current concepts. Parkinsonism Relat Disord. 2014;20:S113–7.PubMedCrossRefGoogle Scholar
  140. 140.
    Waln O, Jankovic J. Zolpidem improves tardive dyskinesia and akathisia. Mov Disord. 2013;28:1748–9.PubMedCrossRefGoogle Scholar
  141. 141.
    Jankovic J. An update on new and unique uses of botulinum toxin in movement disorders. Toxicon. 2017. Scholar
  142. 142.
    Tan EK, Jankovic J. Tardive and idiopathic oromandibular dystonia: a clinical comparison. J Neurol Neurosurg Psychiatry. 2000;68:186–90.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Morigaki R, Mure H, Kaji R, Nagahiro S, Goto S. Therapeutic perspective on tardive syndrome with special reference to deep brain stimulation. Front Psychiatry. 2016;7:207.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Sun B, Chen S, Zhan S, Le W, Krahl SE. Subthalamic nucleus stimulation for primary dystonia and tardive dystonia. Acta Neurochir Suppl. 2007;97:207–14.PubMedCrossRefGoogle Scholar
  145. 145.
    Meng D-W, Liu H-G, Yang A-C, Zhang K, Zhang J-G. Long-term effects of subthalamic nucleus deep brain stimulation in tardive dystonia. Chin Med J (Engl). 2016;129:1257–8.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Yasui-Furukori N, Nakamura K, Katagai H, Kaneko S. The effects of electroconvulsive therapy on tardive dystonia or dyskinesia induced by psychotropic medication: a retrospective study. Neuropsychiatr Dis. Treat. 2014;10:1209–12.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Peng L-Y, Lee Y, Lin P-Y. Electroconvulsive therapy for a patient with persistent tardive dyskinesia. J ECT. 2013;29:e52–4.PubMedCrossRefGoogle Scholar
  148. 148.
    Manteghi A, Hojjat SK, Javanbakht A. Remission of tardive dystonia with electroconvulsive therapy. J Clin Psychopharmacol. 2009;29:314–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018
corrected publication March 2018

Authors and Affiliations

  1. 1.Parkinson’s Disease Center and Movement Disorders Clinic, Department of NeurologyBaylor College of MedicineHoustonUSA

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