Skip to main content
SpringerLink
Log in

Drug-Induced Dyskinesia, Part 2: Treatment of Tardive Dyskinesia

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. The main types of drug-induced dyskinesias include levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease and tardive syndrome (TS), typically present in patients with psychiatric or gastrointenstinal disorders treated with dopamine receptor blocking drugs, also referred to as neuroleptics. Besides preventive measures (i.e., avoiding the use of the offending drugs), general treatment strategies include slow taper of the offending agent and use of dopamine-depleting agents like tetrabenazine. Botulinum toxin may be helpful for wearing off focal dystonia and some forms of tardive dystonia. Deep brain stimulation is usually reserved for patients with disabling motor fluctuations, LID, and for severe TS that cannot be managed medically.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Loonen AJMAJ. New insights into the mechanism of drug-induced dyskinesia. CNS spectrums. 2013;18(1):15.

    Article  PubMed  Google Scholar 

  2. Walters AS, McHale D, Sage JI, Hening WA, Bergen M. A blinded study of the suppressibility of involuntary movements in Huntington’s chorea, tardive dyskinesia, and L-dopa-induced chorea. Clin Neuropharmacol. 1990;13(3):236–40.

    Article  CAS  PubMed  Google Scholar 

  3. Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov. 2013;12(3):03–161.

    Google Scholar 

  4. Reich SG. Pearls: hyperkinetic movement disorders. Semin Neurol. 2010;30(1):15–22.

    Article  PubMed  Google Scholar 

  5. Cloud LJ, Zutshi D, Factor SA. Tardive dyskinesia: therapeutic options for an increasingly common disorder. Neurotherapeutics. 2014;11(1):166–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Patel N, Jankovic J, Hallett M. Sensory aspects of movement disorders. Lancet Neurol. 2014;13(1):100–12.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Anand VS, Dewan MJ. Withdrawal-emergent dyskinesia in a patient on risperidone undergoing dosage reduction. Ann Clin Psychiatry. 1996;8(3):179–82.

    Article  CAS  PubMed  Google Scholar 

  8. American Psychiatric Association. Medication-induced movement disorders and other adverse effects of medication. Diagnostic and statistical manual of mental disorders, Fifth edn: American Psychiatric Association; 2013.

  9. Mejia NI, Jankovic J. Tardive dyskinesia and withdrawal emergent syndrome in children. Expert Rev Neurother. 2010;10(6):893–901.

    Article  PubMed  Google Scholar 

  10. Karama S, Lal S. Tardive dyskinesia following brief exposure to risperidone–a case study. Eur Psychiatry. 2004;19(6):391–2.

    Article  PubMed  Google Scholar 

  11. 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. 2015. doi:10.1002/gps.4399

    Google Scholar 

  12. Novick D, Haro JM, Bertsch J, Haddad PM. Incidence of extrapyramidal symptoms and tardive dyskinesia in schizophrenia: thirty-six-month results from the European schizophrenia outpatient health outcomes study. J Clin Psychopharmacol. 2010;30(5):531–40.

    Article  PubMed  Google Scholar 

  13. Aquino CC, Lang AE. Tardive dyskinesia syndromes: current concepts. Parkinsonism Relat Disord. 2014;20(Suppl 1):S113–7.

    Article  PubMed  Google Scholar 

  14. Kiriakakis V, Bhatia KP, Quinn NP, Marsden CD. The natural history of tardive dystonia. A long-term follow-up study of 107 cases. Brain J Neurol. 1998;121(Pt 11):2053–66.

    Article  Google Scholar 

  15. Correll CU, Schenk EM. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry. 2008;21(2):151–6.

    Article  PubMed  Google Scholar 

  16. Jankovic J. Bradley’s Neurology in Clinical Practice 2012.

  17. Lehosit JBP, Fermina, Dhanya V, Leslie C. Tardive Dyskinesia. Wiley: Chichester. 2015.

  18. Correll CUCU. Tardive dyskinesia and new antipsychotics. Curr Opin Psychiatry. 2008;21(2):151–6.

    Article  PubMed  Google Scholar 

  19. 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(3):414–25.

    Article  PubMed  Google Scholar 

  20. Kinon BJ, Kollack-Walker S, Jeste D, Gupta S, Chen L, Case M, 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.

    Article  PubMed  Google Scholar 

  21. Lee PE, Sykora K, Gill SS, Mamdani M, Marras C, Anderson G, et al. Antipsychotic medications and drug-induced movement disorders other than parkinsonism: a population-based cohort study in older adults. J Am Geriatr Soc. 2005;53(8):1374–9.

    Article  PubMed  Google Scholar 

  22. Rosenheck RA. Evaluating the cost-effectiveness of reduced tardive dyskinesia with second-generation antipsychotics. Br J Psychiatry J Mental Sci. 2007;191:238–45.

    Article  CAS  Google Scholar 

  23. Rosenheck R, Cramer J, Xu W, Thomas J, Henderson W, Frisman L, et al. A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia. N Engl J Med. 1997;337(12):809–15.

    Article  CAS  PubMed  Google Scholar 

  24. Rosenheck R, Perlick D, Bingham S, Liu-Mares W, Collins J, Warren S, et al. Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial. JAMA. 2003;290(20):2693–702.

    Article  CAS  PubMed  Google Scholar 

  25. Obeso JA. The Movement Disorders journal 2016 and onward. Mov Disord. 2016;31(1):1–2 (Epub 2016/01/11).

    Article  PubMed  Google Scholar 

  26. Adrianzen C, Arango-Davila C, Araujo DM, Ruiz I, Walton RJ, Dossenbach M, et al. Relative association of treatment-emergent adverse events with quality of life of patients with schizophrenia: post hoc analysis from a 3-year observational study. Hum Psychopharmacol. 2010;25(6):439–47.

    Article  PubMed  Google Scholar 

  27. Farah A. Atypicality of atypical antipsychotics. Prim Care Companion J Clin Psychiatry. 2005;7(6):268–74.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis. Am J Psychiatry. 2001;158(3):360–9.

    Article  CAS  PubMed  Google Scholar 

  29. Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P. A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry. 2000;57(6):553–9.

    Article  CAS  PubMed  Google Scholar 

  30. Standaert DG, Galanter JM. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy: Lippincott Williams & Wilkins, 2008.

  31. Pena MS, Yaltho TC, Jankovic J. Tardive dyskinesia and other movement disorders secondary to aripiprazole. Mov Disord. 2011;26(1):147–52.

    Article  PubMed  Google Scholar 

  32. Casey DE. Tardive dyskinesia: pathophysiology and animal models. J Clin Psychiatry. 2000;4:5–9.

    Google Scholar 

  33. Corson PW, Nopoulos P, Miller DD, Arndt S, Andreasen NC. Change in basal ganglia volume over 2 years in patients with schizophrenia: typical versus atypical neuroleptics. Am J Psychiatry. 1999;156(8):1200–4.

    CAS  PubMed  Google Scholar 

  34. Ogawa T, Nagao T, Kashiwabara K, Fujiwara Y, Harada T, Otsuki S. Tardive dyskinesia and neurotransmitters: effects of sodium valproate, cyproheptadine, oxypertine, hydroxyzine pamoate and Ca-hopantenate on monoamine metabolites, cyclic nucleotides and gamma-aminobutyric acid in human cerebrospinal fluid. Clin Ther. 1984:1–17.

  35. Mizuno Y. Parkinson’s Disease: CRC Press, 2012.

  36. Aia PG, Revuelta GJ, Cloud LJ, Factor SA. Tardive dyskinesia. Curr Treat Options Neurol. 2011;13(3):231–41.

    Article  PubMed  Google Scholar 

  37. 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.

    Article  CAS  PubMed  Google Scholar 

  38. Modestin J, Wehrli MV, Stephan PL, Agarwalla P. Evolution of neuroleptic-induced extrapyramidal syndromes under long-term neuroleptic treatment. Schizophr Res. 2008;100(1–3):97–107.

    Article  PubMed  Google Scholar 

  39. Fernandez HH, Krupp B, Friedman JH. The course of tardive dyskinesia and parkinsonism in psychiatric inpatients: 14-year follow-up. Neurology. 2001;56(6):805–7.

    Article  CAS  PubMed  Google Scholar 

  40. 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(1):49–55.

    Article  CAS  PubMed  Google Scholar 

  41. Bhidayasiri R, Fahn S, Weiner WJ, Gronseth GS, Sullivan KL, Zesiewicz TA. Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;81(5):463–9.

    Article  PubMed  Google Scholar 

  42. Hazari N, Kate N, Grover S. Clozapine and tardive movement disorders: a review. Asian J Psychiatr. 2013;6(6):439–51.

    Article  PubMed  Google Scholar 

  43. Jankovic J, Clarence-Smith K. Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders. Expert Rev Neurother. 2011;11(11):1509–23.

    Article  CAS  PubMed  Google Scholar 

  44. Ondo WG, Hanna PA, Jankovic J. Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol. Am J Psychiatry. 1999;156(8):1279–81.

    CAS  PubMed  Google Scholar 

  45. Kazamatsuri H, Chien CP, Cole JO. Long-term treatment of tardive dyskinesia with haloperidol and tetrabenazine. Am J Psychiatry. 1973;130(4):479–83.

    CAS  PubMed  Google Scholar 

  46. Chen JJ, Ondo WG, Dashtipour K, Swope DM. Tetrabenazine for the treatment of hyperkinetic movement disorders: a review of the literature. Clin Ther. 2012;34(7):1487–504.

    Article  PubMed  Google Scholar 

  47. Jankovic J, Orman J. Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. Neurology. 1988;38(3):391–4.

    Article  CAS  PubMed  Google Scholar 

  48. Shen V, Clarence-Smith K, Hunter C, Jankovic J. Safety and efficacy of tetrabenazine and use of concomitant medications during long-term, open-label treatment of chorea associated with huntington’s and other diseases. Tremor Other Hyperkinet Mov. 2013;22(3):03–191.

    Google Scholar 

  49. Kenney C, Hunter C, Mejia N, Jankovic J. Is history of depression a contraindication to treatment with tetrabenazine? Clin Neuropharmacol. 2006;29(5):259–64 (Epub 2006/09/09).

    Article  CAS  PubMed  Google Scholar 

  50. Stamler D, Bradbury M, Brown F, editors. The pharmacokinetics and safety of deuterated-tetrabenazine. 65th AAN Annual Meeting; 2013; San Diego: Neurology.

  51. Muller T. Valbenazine granted breakthrough drug status for treating tardive dyskinesia. Expert opinion on investigational drugs. 2015;24(6):737–42 (Epub 2015/03/27).

    Article  PubMed  Google Scholar 

  52. 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(12):1681–7.

    Article  PubMed  Google Scholar 

  53. 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):445–51.

    Article  CAS  PubMed  Google Scholar 

  54. Woods SW, Saksa JR, Baker CB, Cohen SJ, Tek C. Effects of levetiracetam on tardive dyskinesia: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2008;69(4):546–54.

    Article  CAS  PubMed  Google Scholar 

  55. Libov I, Miodownik C, Bersudsky Y, Dwolatzky T, Lerner V. Efficacy of piracetam in the treatment of tardive dyskinesia in schizophrenic patients: a randomized, double-blind, placebo-controlled crossover study. J Clin Psychiatry. 2007;68(7):1031–7.

    Article  CAS  PubMed  Google Scholar 

  56. 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):615–21.

    Article  PubMed  Google Scholar 

  57. Schrodt GR Jr, Wright JH, Simpson R, Moore DP, Chase S. Treatment of tardive dyskinesia with propranolol. J Clin Psychiatry. 1982;43(8):328–31.

    PubMed  Google Scholar 

  58. Waln OO. Zolpidem improves tardive dyskinesia and akathisia. Mov Disord. 2013;28(12):1748–9.

    Article  CAS  PubMed  Google Scholar 

  59. Yasui-Furukori N, Kikuchi A, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Peng LY, Lee Y, Lin PY. Electroconvulsive therapy for a patient with persistent tardive dyskinesia: a case report and literature review. J Ect. 2013;29(3).

  61. Malek-Ahmadi P, Weddige RL. Tardive Dyskinesia and Electroconvulsive Therapy. Convuls Ther. 1988;4(4):328–31.

    PubMed  Google Scholar 

  62. Hennings JM, Krause E, Botzel K, Wetter TC. Successful treatment of tardive lingual dystonia with botulinum toxin: case report and review of the literature. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1167–71.

    Article  CAS  PubMed  Google Scholar 

  63. Beckmann YY, Secil Y, Saka S, Kuserli A, Ciftci Y. Treatment of intractable tardive lingual dyskinesia with botulinum toxin. J Clin Psychopharmacol. 2011;31(2):250–1 (Epub 2011/03/03).

    Article  PubMed  Google Scholar 

  64. Rapaport A, Sadeh M, Stein D, Levine J, Sirota P, Mosheva T, et al. Botulinum toxin for the treatment of oro-facial-lingual-masticatory tardive dyskinesia. Mov Disord. 2000;15(2):352–5.

    Article  CAS  PubMed  Google Scholar 

  65. Tschopp L, Salazar Z, Micheli F. Botulinum toxin in painful tardive dyskinesia. Clin Neuropharmacol. 2009;32(3):165–6.

    Article  PubMed  Google Scholar 

  66. van Harten PN, Hovestadt A. Botulinum toxin as a treatment for tardive dyskinesia. Mov Disord. 2006;21(8):1276–7.

    Article  PubMed  Google Scholar 

  67. Spindler MA, Galifianakis NB, Wilkinson JR, Duda JE. Globus pallidus interna deep brain stimulation for tardive dyskinesia: case report and review of the literature. Parkinsonism Relat Disord. 2013;19(2):141–7.

    Article  PubMed  Google Scholar 

  68. Kefalopoulou Z, Paschali A, Markaki E, Vassilakos P, Ellul J, Constantoyannis C. A double-blind study on a patient with tardive dyskinesia treated with pallidal deep brain stimulation. Acta Neurol Scand. 2009;119(4):269–73.

    Article  CAS  PubMed  Google Scholar 

  69. Damier P, Thobois S, Witjas T, Cuny E, Derost P, Raoul S, et al. Bilateral deep brain stimulation of the globus pallidus to treat tardive dyskinesia. Arch Gen Psychiatry. 2007;64(2):170–6.

    Article  PubMed  Google Scholar 

  70. Sun B, Chen S, Zhan S, Le W, Krahl SE. Subthalamic nucleus stimulation for primary dystonia and tardive dystonia. Acta Neurochir Suppl. 2007;97(Pt 2):207–14.

    Article  CAS  PubMed  Google Scholar 

  71. Zhang JG, Zhang K, Wang ZC, Ge M, Ma Y. Deep brain stimulation in the treatment of secondary dystonia. Chin Med J. 2006;119(24):2069–74.

    PubMed  Google Scholar 

  72. 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(4):510–4.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Parkinson’s Disease Center and Movement Disorders Clinic, Baylor College of Medicine, 7200 Cambridge, Suite 9A, Houston, TX, 77030-4202, USA

    Dhanya Vijayakumar & Joseph Jankovic

Authors
  1. Dhanya Vijayakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph Jankovic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph Jankovic.

Ethics declarations

Funding

None.

Conflict of interest

Dr. Jankovic has received grants from Adamas Pharmaceuticals, Inc.; Allergan, Inc.; CHDI Foundation; Civitas/Acorda Therapeutics; Huntington Study Group; Ipsen Limited; Kyowa Haako Kirin Pharma, Inc.; Lundbeck Inc.; Medtronic; Merz Pharmaceuticals; Michael J. Fox Foundation for Parkinson Research; National Institutes of Health; National Parkinson Foundation; Omeros Corporation; Parkinson Study Group; Pfizer; Prothena Biosciences Inc.; Psyadon Pharmaceuticals, Inc.; St. Jude Medical; and Teva Pharmaceutical Industries Ltd. Dr. Jankovic receives consulting fees from Adamas Pharmaceuticals, Inc.; Allergan, Inc.; and Teva Pharmaceutical Industries Ltd. Dr. Jankovic has received royalties from Cambridge; Elsevier; Future Science Group; Hodder Arnold; Lippincott Williams and Wilkins; and Wiley-Blackwell. Dhanya Vijayakumar, MD, has no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vijayakumar, D., Jankovic, J. Drug-Induced Dyskinesia, Part 2: Treatment of Tardive Dyskinesia. Drugs 76, 779–787 (2016). https://doi.org/10.1007/s40265-016-0568-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-016-0568-1

Keywords

Search

Navigation