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Department of Neurology

Houston, Texas

BCM neurologists see patients through the Baylor Clinic and some of the world's leading specialty clinics.
Department of Neurology
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Tetrabenazine (TBZ)

Movement disorders are neurological conditions manifested either by slowness of movement, seen in Parkinson’s disease, or abnormal involuntary movements, the so-called hyperkinesias (hyper: too much, kinesis: movement). The hyperkinesias are characterized by excessive, involuntary, repetitive, twisting or random jerk-like move­ments which may involve the face, limbs, or the entire body. One form of hyperkinesias is tardive dyskinesia, manifested typically by repetitive, chewing mouth and jaw movements. Repetitive (stereotypic) movements associated with tardive dyskinesia may also involve the trunk (rocking movements) and limbs. Tardive dyskinesia is caused by exposure to certain antipsychotics (medications used to treat hallucinations and disorders of thinking) or antiemetics (medications against nausea an vomiting). Although often transient, tardive dyskinesia may be permanent. Other examples of hyperkinesias include chorea (which means dance in Greek, and are brief, irregular muscle contractions that appear to flow from one muscle to the next, as seen in conditions such as Huntington disease), athetosis (subtle twisting and writhing movements often accompanying chorea, seen for example in cerebral palsy), ballism (large amplitude, flinging movements usually of one arm or leg, most commonly following a lesion, such as a stroke, in a specific region in the brain), tics (e.g. Tourette syndrome), dystonia (sustained muscle contractions causing twisting and abnormal postures), myoclonus (brief muscle jerks), stereotypies (constant repetition of certain gestures and movements such as seen in children with developmental disorders) and akathisia (subjective feeling of “inner” restlessness and inability to stay still).

The neurochemical alterations underlying involuntary movement disorders have not been well-defined, and the pharmacologic strategies used to correct the abnormalities are speculative. Dopamine is one of the many neurotransmitters found in the brain. An excess of dopamine or an increased sensitivity of the cell receptors to dopamine is thought to play a dominant role in many hyperkinetic movement disorders, particularly tardive dyskinesia, Huntington disease and Tourette syndrome. The antipsychotic or antiemetic drugs block the dopamine receptors and are sometimes used to treat the various hyperkinetic movement disorders. However, these drugs carry the risk of tardive dyskinesia and, therefore, are not appropriate for the chronic therapy of movement disorders. Other drugs that act by reducing the dopaminergic transmission and thus ameliorate hyperkinesias include reserpine and tetrabenazine (TBZ). Both drugs cause depletion of dopamine in the brain, but reserpine also causes dopamine depletion in the peripheral nervous system and, therefore, may cause low blood pressure. The primary pharmacologic action of TBZ is depletion of dopamine in the central nervous system by inhibiting the human vesicular monoamine transporter isoform 2 (hVMAT2).

Although TBZ has not yet been approved in the United States, it has been used in other countries for treatment of tardive dyskinesia and other hyperkinetic movement disorders. In 1979, the Food and Drug Administration (FDA) has granted Dr. Jankovic a special permission (IND) to use TBZ in various movement disorders. Since that time we have accumulated long-term experience with this drug in well over thousand patients. Based on this experience over the past quarter century, as well as double-blind and open label studies, we conclude that TBZ is most effective and best tolerated treatment for tardive dyskinesia and some other hyperkinetic movement disorders, especially Hungtington disease and Tourette Syndrome. The most common side effects included drowsiness (25.0%), parkinsonism manifested mainly by slowness of movement and tremors (15.4%), depression (7.6%), insomnia (5.0%), and nervousness/anxiety/ restlessness (7.6%). The side effects are reversible and are usually controlled by reducing the dose. There has been no report of tetrabenazine-induced tardive dyskinesia, and, therefore, this depleting agent has a distinct advantage over the dopamine-blocking agents (typical neuroleptics) in the treatment of a variety of hyperkinetic movement disorders.

The treatment with TBZ is provided as a service to the patients seen in the Movement Disorders Clinic at Baylor College of Medicine and is not considered research. Each patient will be carefully evaluated (and videotaped) prior to the institution of the drug and will sign an informed consent for the videotaping and the drug use. They will be re-evaluated periodically as needed. Patients will be required to pay the current price for the medication and for their medical care by the physician. It is Baylor’s policy not to reimburse for returned medication, even if the bottle(s) was (were) never opened. Although it is possible that TBZ will be eventually available for clinical use in the U.S.A., the drug is currently considered investiga­tional in this country. Cambridge Laboratories of U.K., the sole worldwide distributor of TBZ, however, is able to supply the drug directly to the patient or his/her physician on a named patient basis under section 9-71-30C of the FDA regulations for pharmaceuticals imported for personal use. A prescription and a letter from the patient’s physician requesting TBZ is sufficient to import the drugs to the USA. The drug is currently marketed in the U.K. by Cambridge under the brand name Xenazine™ 25. (The old brand name was Nitoman).

Selected References

  • Hunter CB, Vuong KD, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Neurology 2004;62 (Suppl 5): A506-7.
  • Hunter CB, Vuong K, Mejia N, Jankovic J. Tetrabenazine, a monoamine depleter, effective in the treatment of Tourette syndrome. Mov Disord 2004;19(Suppl 9):S437.
  • Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66(3):366-72.
  • Jain S, Greene PE, Frucht SJ. Tetrabenazine therapy of pediatric hyperkinetic movement disorders. Mov Disord 2006;21:1966-72.
  • Jankovic J. Treatment of hyperkinetic movement disorders with tetrabenazine: A double-blind crossover study. Ann Neurol 1982;11:41-47.
  • Jankovic J. Tardive syndromes and other drug-induced movement disorders. Clin Neuropharmacol 1995;18:197-214.
  • Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology 1997;48:358-362.
  • Jankovic J, Hunter CB, Mejia N, Vuong K. Tetrabenazine: Effective treatment for tardive dyskinesia. Mov Disord 2004;19(Suppl 9):S73.
  • Jankovic J, Vuong KD, Hunter C. Safety and efficacy of tetrabenazine in the treatment of Huntington’s disease and other choreas. Mov Disord 2004;19:1127.
  • Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord 2007;22:193-7.
  • Kenney C, Hunter C, Davidson A, Jankovic J. Short-term effects of tetrabenazine on chorea associated with Huntington's disease. Mov Disord 2007;22:10-3.
  • Kenney C, Hunter C, Mejia N, Jankovic J. Is history of depression a contraindication to treatment with tetrabenazine? Clin Neuropharmacol 2006;29:259-64.
  • Kenney C, Jankovic J. Tetrabenazine in the treatment of hyperkinetic movement disorders.
  • Expert Rev Neurother 2006;6:7-17. Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Movement Disorders. 2007; 22(2):193-7.
  • Ondo WG, Hanna PA, Jankovic J. Tetrabenazine treatment for tardive dyskinesia: Assessment by randomized videotape protocol. Am J Psychiatry 1999;156:1279-1281.
  • Ondo WG, Tintner R, Thomas M, Jankovic J. Tetrabenazine treatment for Huntington’s disease-associated chorea. Clin Neuropharmacol 2002;25:300-302.
  • Paleacu D, Giladi N, Moore O, Stern A, Honigman S, Badarny S. Tetrabenazine treatment in movement disorders.Clin Neuropharmacol 2004;27:230-3.

Appendix

For further information about the manufacturing and distribution of TBZ you can contact:

Cambridge Laboratories
Deltic House
Kingfisher Way
Silverlink Business Park
Wallsend
Tyne & Wear
NE28 9NX
Email: marketing@camb-labs.com
www.camb-labs.com

  •  TelFax
  • Customer Service+44 191 2969 300 or -370+44 191 2969 368
  • Marketing+44 191 2969 340+44 191 2969 370
  • Switchboard+44 191 2969 369+44 191 2969 368
  • Directorate+44 191 2969 370+44 191 2969 379

Prestwick Scientific Capital, Inc
1825 K Street N.W., Suite 1475
Wahington, DC 20006 USA
Tel: 202-261-3261, 202-296-1400
Fax: 202-296-7450

For additional information visit http://www.bcm.edu/neurology/pdcmdc/