Clinical Drug Investigation

, Volume 28, Issue 7, pp 443–459 | Cite as

Tourette’s Syndrome and Role of Tetrabenazine

Review and Personal Experience
  • Mauro PortaEmail author
  • Marco Sassi
  • Mario Cavallazzi
  • Maurizio Fornari
  • Arianna Brambilla
  • Domenico Servello
Review Article


Gilles de la Tourette’s syndrome (Tourette’s syndrome; TS) is an inherited tic disorder commonly associated with other neurobehavioural conditions such as attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While the clinical presentation of TS and other features of this disorder have been well characterized, the genetic and neurobiological basis of the disease remains incompletely elucidated. The suggestion of a central role of dopamine in the aetiology of TS has been made on the basis of experimental studies, evidence from neuroimaging studies and the therapeutic response patients with TS have to agents that antagonize or interfere with putative dopaminergic pathways. Tetrabenazine is such an agent; it depletes presynaptic dopamine and serotonin stores and blocks postsynaptic dopamine receptors. In clinical studies, tetrabenazine has been found to be effective in a wide range of hyperkinetic movement disorders, including small numbers (<50) of patients with TS in some studies. Results of a retrospective chart review enrolling only patients with TS (n = 77; mean age ≈15 years) showed that 2 years’ treatment with tetrabenazine resulted in an improvement in functioning and TS-related symptoms in over 80% of patients, findings that suggest that treatment with tetrabenazine may have long-term benefits. The authors’ experience with 120 heavily co-medicated patients with TS confirms these findings. Long-term (mean 19 months) tetrabenazine treatment resulted in a Clinical Global Impressions of Change scale rating of ‘improved’ in 76% of patients. Such findings are promising and suggest that tetrabenazine may be suitable as add-on therapy in patients for whom additional suppression of tics is required.


Neuroleptic Malignant Syndrome Tetrabenazine Acute Dystonic Reaction Postsynaptic Dopamine Receptor Hyperkinetic Movement Disorder 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Editorial support for this manuscript was provided by the Medical Communications Group, Wolters Kluwer Health, Pharma Solutions Division. Medical writers were involved in the initial literature search and drafting of materials prior to a review and redrafting by Prof. Porta. The medical writing of the review part of this article and not the personal experience section was funded by an educational grant from Chiesi Italia. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Chowdhury U, Heyman I. Tourette’s syndrome in children. BMJ 2004; 329(7479): 1356–7PubMedCrossRefGoogle Scholar
  2. 2.
    Muller N. Tourette’s syndrome: clinical features, pathophysiology, and therapeutic approaches. Dialogues Clin Neurosci 2007; 9(2): 161–71PubMedGoogle Scholar
  3. 3.
    Bruun RD. Gilles de la Tourette’s syndrome: an overview of clinical experience. J Am Acad Child Psych 1984; 23(2): 126–33CrossRefGoogle Scholar
  4. 4.
    Apter A, Pauls DL, Bleich A, et al. An epidemiologic study of Gilles de la Tourette’s syndrome in Israel. Arch Gen Psych 1993; 50(9): 734–8CrossRefGoogle Scholar
  5. 5.
    Singer HS. Tourette’s syndrome: from behaviour to biology. Lancet Neurology 2005; 4(3): 149–59PubMedGoogle Scholar
  6. 6.
    Kurlan R, McDermott MP, Deeley C, et al. Prevalence of tics in schoolchildren and association with placement in special education. Neurology 2001; 57(8): 1383–8PubMedCrossRefGoogle Scholar
  7. 7.
    Coffey BJ, Park KS. Behavioral and emotional aspects of Tourette syndrome. Neurol Clin 1997; 15(2): 277–89PubMedCrossRefGoogle Scholar
  8. 8.
    Swain JE, Scahill L, Lombroso PJ, et al. Tourette syndrome and tic disorders: a decade of progress. J Am Acad Child Adolesc Psych 2007; 46(8): 947–68CrossRefGoogle Scholar
  9. 9.
    Robertson MM, Stern JS. Gilles de la Tourette syndrome: symptomatic treatment based on evidence. Eur Child Adolesc Psychiatry 2000; 9Suppl. 1: 160–75Google Scholar
  10. 10.
    Robertson MM. Attention deficit hyperactivity disorder, tics and Tourette’s syndrome: the relationship and treatment implications. A commentary. Eur Child Adolesc Psychiatry 2006 Feb; 15(1): 1–11PubMedCrossRefGoogle Scholar
  11. 11.
    Como PG, LaMarsh J, O’Brien KA. Obsessive-compulsive disorder in Tourette’s syndrome. Advances Neurol 2005; 96: 249–61Google Scholar
  12. 12.
    Goodman WK, Storch EA, Geffken GR, et al. Obsessive-compulsive disorder in Tourette syndrome. J Child Neurol 2006; 21(8): 704–14PubMedCrossRefGoogle Scholar
  13. 13.
    Robertson MM, Banerjee S, Eapen V, et al. Obsessive compulsive behaviour and depressive symptoms in young people with Tourette syndrome: a controlled study. Eur Child Adolesc Psychiatry 2002; 11(6): 261–5PubMedCrossRefGoogle Scholar
  14. 14.
    Robertson MM, Williamson F, Eapen V. Depressive symptomatology in young people with Gilles de la Tourette syndrome: a comparison of self-report scales. J Affect Dis 2006; 91(2–3): 265–8PubMedCrossRefGoogle Scholar
  15. 15.
    Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. Brain 2000; 123 (Pt 3): 425–62PubMedCrossRefGoogle Scholar
  16. 16.
    Zinner S. Tourette syndrome: more than just tics (part 2). Contemporary Paediatrics 2004; 21(8): 38–49Google Scholar
  17. 17.
    Coffey B, Frazier J, Chen S. Comorbidity, Tourette syndrome, and anxiety disorders. Adv Neurol 1992; 58: 95–104PubMedGoogle Scholar
  18. 18.
    Keen-Kim D, Freimer NB. Genetics and epidemiology of Tourette syndrome. J Child Neurol 2006; 21(8): 665–71PubMedCrossRefGoogle Scholar
  19. 19.
    Pauls DL. Update on the genetics of Tourette syndrome. Adv Neurol 2001; 85: 281–93PubMedGoogle Scholar
  20. 20.
    Leckman JF, Dolnansky ES, Hardin MT, et al. Perinatal factors in the expression of Tourette’s syndrome: an exploratory study. J Am Acad Child Adolescent Psych 1990; 29(2): 220–6CrossRefGoogle Scholar
  21. 21.
    Leckman JF, Price RA, Walkup JT, et al. Nongenetic factors in Gilles de la Tourette’s syndrome. Arch Gen Psych 1987; 44(1): 100CrossRefGoogle Scholar
  22. 22.
    Church AJ, Dale RC, Lees AJ, et al. Tourette’s syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psych 2003; 74(5): 602–7CrossRefGoogle Scholar
  23. 23.
    Mell LK, Davis RL, Owens D. Association between streptococcal infection and obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder. Pediatrics 2005; 116(1): 56–60PubMedCrossRefGoogle Scholar
  24. 24.
    Hoekstra PJ, Anderson GM, Limburg PC, et al. Neurobiology and neuroimmunology of Tourette’s syndrome: an update. Cellular Molecular Life sci 2004; 61(7–8): 886–98Google Scholar
  25. 25.
    Berardelli A, Curra A, Fabbrini G, et al. Pathophysiology of tics and Tourette syndrome. J Neurol 2003; 250(7): 781–7PubMedCrossRefGoogle Scholar
  26. 26.
    Singer HS, Minzer K. Neurobiology of Tourette’s syndrome: concepts of neuroanatomic localisation and neurochemical abnormalities. Brain Dev 2003; 25Suppl. 1: S70–84PubMedCrossRefGoogle Scholar
  27. 27.
    Frey KA, Albin RL. Neuroimaging of Tourette syndrome. J Child Neurol 2006; 21(8): 672–7PubMedCrossRefGoogle Scholar
  28. 28.
    Saka E, Graybiel AM. Pathophysiology of Tourette’s syndrome: striatal pathways revisited. Brain Dev 2003; 25Suppl. 1: S15–9PubMedCrossRefGoogle Scholar
  29. 29.
    Peterson BS, Skudlarski P, Anderson AW, et al. A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psych 1998; 55(4): 326–33CrossRefGoogle Scholar
  30. 30.
    Serrien DJ, Orth M, Evans AH, et al. Motor inhibition in patients with Gilles de la Tourette syndrome: functional activation patterns as revealed by EEG coherence. Brain 2005; 128 (Pt 1): 116–25PubMedCrossRefGoogle Scholar
  31. 31.
    Francois C, Grabli D, McCairn K, et al. Behavioural disorders induced by external globus pallidus dysfunction in primates: II. Anatomical study. Brain 2004; 127 (Pt 9): 2055–70PubMedCrossRefGoogle Scholar
  32. 32.
    Grabli D, McCairn K, Hirsch EC, et al. Behavioural disorders induced by external globus pallidus dysfunction in primates: I. Behavioural study. Brain 2004; 127 (Pt 9): 2039–54PubMedCrossRefGoogle Scholar
  33. 33.
    American Psychiatric Association. Task force on DSM-IV. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994; xxvii: 886Google Scholar
  34. 34.
    Jankovic, J. Diagnosis and classification of tics and Tourette syndrome. Adv Neurol 1992; 58: 7–14PubMedGoogle Scholar
  35. 35.
    Gaze C, Kepley HO, Walkup JT. Co-occurring psychiatric disorders in children and adolescents with Tourette syndrome. J Child Neurol 2006; 21(8): 657–64PubMedCrossRefGoogle Scholar
  36. 36.
    Robertson MM, Trimble MR, Lees AJ. Self-injurious behaviour and the Gilles de la Tourette syndrome: a clinical study and review of the literature. Psychol Med 1989; 19(3): 611–25PubMedCrossRefGoogle Scholar
  37. 37.
    Mathews CA, Waller J, Glidden D, et al. Self injurious behaviour in Tourette syndrome: correlates with impulsivity and impulse control. J Neurol Neurosurg Psychiatry 2004; 75(8): 1149–55PubMedCrossRefGoogle Scholar
  38. 38.
    Chatterjee A, Frucht SJ. Tetrabenazine in the treatment of severe pediatric chorea. Mov Disord 2003; 18(6): 703–6PubMedCrossRefGoogle Scholar
  39. 39.
    Jain S, Greene PE, Frucht SJ. Tetrabenazine therapy of pediatric hyperkinetic movement disorders. Mov Disord 2006; 21(11): 1966–72PubMedCrossRefGoogle Scholar
  40. 40.
    Ondo WG, Hanna PA, Jankovic J. Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol. Am J Psychiatry 1999; 156(8): 1279–81PubMedGoogle Scholar
  41. 41.
    Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology 2006; 66(3): 366–72CrossRefGoogle Scholar
  42. 42.
    Kenney C, Hunter C, Davidson A, et al. Short-term effects of tetrabenazine on chorea associated with Huntington’s disease. Mov Disord 2007; 22(1): 10–3PubMedCrossRefGoogle Scholar
  43. 43.
    Sitburana O, Ondo WG. Tetrabenazine for hyperglycemic-in-duced hemichorea-hemiballismus. Mov Disord 2006; 21(11): 2023–5PubMedCrossRefGoogle Scholar
  44. 44.
    Vieregge P. Tetrabenazine in the treatment of senile vocal tics. J Neurol 1987; 235(2): 126–7PubMedCrossRefGoogle Scholar
  45. 45.
    Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology 1997; 48(2): 358–62PubMedCrossRefGoogle Scholar
  46. 46.
    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: 103–9PubMedGoogle Scholar
  47. 47.
    Butler PD, Edwards E, Barkai AI. Imipramine and tetrabenazine: effects on monoamine receptor binding sites and phosphoinositide hydrolysis. Eur J Pharmacol 1989; 160(1): 93–100PubMedCrossRefGoogle Scholar
  48. 48.
    Tomlinson DR. The mode of action of tetrabenazine on peripheral noradrenergic nerves. Br J Pharmacol 1977; 61(3): 339–44PubMedCrossRefGoogle Scholar
  49. 49.
    Login IS, Cronin MJ, Harcus CT, et al. Neuroendocrine evidence that tetrabenazine is a dopamine antagonist. Proc Soc Exp Biol Med 1983; 172(2): 225–31PubMedGoogle Scholar
  50. 50.
    Login IS, Cronin MJ, MacLeod RM. Tetrabenazine has properties of a dopamine receptor antagonist. Ann Neurol 1982; 12(3): 257–62PubMedCrossRefGoogle Scholar
  51. 51.
    Reches A, Burke RE, Kuhn CM, et al. Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain. J Pharmacol Exp Ther 1983; 225(3): 515–21PubMedGoogle Scholar
  52. 52.
    Mehvar R, Jamali F. Concentration-effect relationships of tetrabenazine and dihydrotetrabenazine in the rat. J Pharm sci 1987; 76(6): 461–5PubMedCrossRefGoogle Scholar
  53. 53.
    Zheng G, Dwoskin LP, Crooks PA. Vesicular monoamine transporter 2: role as a novel target for drug development. AAPS J 2006 Nov 10; 8(4): E682–92PubMedCrossRefGoogle Scholar
  54. 54.
    Pettibone DJ, Totaro JA, Pflueger AB. Tetrabenazine-induced depletion of brain monoamines: characterization and interaction with selected antidepressants. Eur J Pharmacol 1984; 102(3–4): 425–30PubMedCrossRefGoogle Scholar
  55. 55.
    Mehvar R, Jamali F, Watson MW, et al. Pharmacokinetics of tetrabenazine and its major metabolite in man and rat: bioavail-ability and dose dependency studies. Drug Metab Dispos 1987; 15(2): 250–5PubMedGoogle Scholar
  56. 56.
    Roberts MS, McLean S, Millingen KS, et al. The pharmacokinetics of tetrabenazine and its hydroxy metabolite in patients treated for involuntary movement disorders. Eur J Clin Pharmacol 1986; 29(6): 703–8PubMedCrossRefGoogle Scholar
  57. 57.
    Silay YS, Jankovic J. Emerging drugs in Tourette syndrome. Expert Opinion Emerging Drugs 2005; 10(2): 365–80CrossRefGoogle Scholar
  58. 58.
    Scahill L, Erenberg G, Berlin Jr CM, et al. Contemporary assessment and pharmacotherapy of Tourette syndrome. NeuroRx 2006; 3(2): 192–206PubMedCrossRefGoogle Scholar
  59. 59.
    Kenney CJ, Hunter CB, Mejia NI, et al. Tetrabenazine in the treatment of Tourette syndrome. J Ped Neurol 2007; 5(1): 9–13Google Scholar
  60. 60.
    Bartels M, Zeller E. Tetrabenazine (Nitoman) therapy of chronic spontaneous oral dyskinesia: a video- and EMG-controlled study. Eur Arch Psychiatry Neurol sci 1984; 234(3): 172–4PubMedCrossRefGoogle Scholar
  61. 61.
    Hrachovy RA, Frost Jr JD, Glaze DG. Treatment of infantile spasms with tetrabenazine. Epilepsia 1988; 29(5): 561–3PubMedCrossRefGoogle Scholar
  62. 62.
    Jankovic J. Treatment of hyperkinetic movement disorders with tetrabenazine: a double-blind crossover study. Ann Neurol 1982; 11(1): 41–7PubMedCrossRefGoogle Scholar
  63. 63.
    Jankovic J, Glaze DG, Frost Jr JD. Effect of tetrabenazine on tics and sleep of Gilles de la Tourette’s syndrome. Neurology 1984; 34(5): 688–92PubMedCrossRefGoogle Scholar
  64. 64.
    Jankovic J, Orman J. Tetrabenazine therapy of dystonia, chorea, tics, and other dyskinesias. Neurology 1988; 38(3): 391–4PubMedCrossRefGoogle Scholar
  65. 65.
    Kenney C, Jankovic J. Tetrabenazine in the treatment of hyperkinetic movement disorders. Expert Rev Neurother 2006; 6(1): 7–17PubMedCrossRefGoogle Scholar
  66. 66.
    Paleacu D, Giladi N, Moore O, et al. Tetrabenazine treatment in movement disorders. Clin Neuropharmacol 2004; 27(5): 230–3PubMedCrossRefGoogle Scholar
  67. 67.
    Sandyk R, Bamford CR, Iacono RP. Sleep disorders in Tourette’s syndrome. Int J Neurosci 1987 Nov; 37(1–2): 59–65PubMedCrossRefGoogle Scholar
  68. 68.
    Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord 2007; 22(2): 193–7PubMedCrossRefGoogle Scholar
  69. 69.
    Mikkelsen BO. Tolerance of tetrabenazine during long-term treatment. Acta Neurol Scand 1983; 68(1): 57–60PubMedCrossRefGoogle Scholar
  70. 70.
    Burke RE, Reches A, Traub MM, et al. Tetrabenazine induces acute dystonic reactions. Ann Neurol 1985; 17(2): 200–2PubMedCrossRefGoogle Scholar
  71. 71.
    Ossemann M, Sindic CJ, Laterre C. Tetrabenazine as a cause of neuroleptic malignant syndrome. Mov Disord 1996; 11(1): 95PubMedCrossRefGoogle Scholar
  72. 72.
    Petzinger GM, Bressman SB. A case of tetrabenazine-induced neuroleptic malignant syndrome after prolonged treatment. Mov Disord 1997; 12(2): 246–8PubMedCrossRefGoogle Scholar
  73. 73.
    Stevens E, Roman A, Houa M, et al. Severe hyperthermia during tetrabenazine therapy for tardive dyskinesia. Intensive Care Med 1998; 24(4): 369–71PubMedCrossRefGoogle Scholar
  74. 74.
    Kenney C, Hunter C, Mejia N, et al. Is history of depression a contraindication to treatment with tetrabenazine? Clin Neuro-pharmacol 2006; 29(5): 259–64Google Scholar
  75. 75.
    Fann WE, Lake CR. Amantadine versus trihexyphenidyl in the treatment of neuroleptic-induced parkinsonism. Am J Psychiatry 1976; 133(8): 940–3PubMedGoogle Scholar
  76. 76.
    Kelly JT, Abuzzahab Sr FS. The antiparkinson properties of amantadine in drug-induced parkinsonism. J Clin Pharmacol New Drugs 1971; 11(3): 211–4PubMedGoogle Scholar
  77. 77.
    Gilbert D. Treatment of children and adolescents with tics and Tourette syndrome. J Child Neurol 2006; 21(8): 690–700PubMedCrossRefGoogle Scholar
  78. 78.
    Kastrup A, Schlotter W, Plewnia C, et al. Treatment of tics in Tourette syndrome with aripiprazole. J Clin Psychopharmacol 2005; 25(1): 94–6PubMedCrossRefGoogle Scholar
  79. 79.
    Kim BN, Lee CB, Hwang JW, et al. Effectiveness and safety of risperidone for children and adolescents with chronic tic or Tourette disorders in Korea. J Child Adolescent Psychopharmacol 2005; 15(2): 318–24CrossRefGoogle Scholar
  80. 80.
    Murphy TK, Bengtson MA, Soto O, et al. Case series on the use of aripiprazole for Tourette syndrome. Intern J Neuropsycho-pharmacol 2005; 8(3): 489–90CrossRefGoogle Scholar
  81. 81.
    Scahill L, Leckman JF, Schultz RT, et al. A placebo-controlled trial of risperidone in Tourette syndrome. Neurology 2003; 60(7): 1130–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Mauro Porta
    • 1
    Email author
  • Marco Sassi
    • 1
  • Mario Cavallazzi
    • 1
  • Maurizio Fornari
    • 1
  • Arianna Brambilla
    • 1
  • Domenico Servello
    • 1
  1. 1.Tourette Clinic and Functional NeurosurgeryIRCCS Galeazzi HospitalMilanItaly

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