Tardive Dystonia Medication

  • Author: Daniel Schneider, MD; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych (UK)   more...
 
Updated: Jan 5, 2011
 

Medication Summary

Tardive dystonia may improve or, rarely, resolve, after discontinuation of neuroleptics; however, the condition is often permanent. Treatment with medications include dopamine-depleting agents, dopamine receptor blocking agents, and anticholinergics. There is a case report of clonazepam being added to clozapine with success, but otherwise there is no evidence that benzodiazepines are particularly useful in this condition. Local botulinum toxin injections have been useful for well-chosen focal dystonias.

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Dopamine-depleting agents

Class Summary

The most effective medications are those that deplete catecholamines (eg, reserpine, tetrabenazine). A study by Kang et al in 1988 showed a 63% response to at least 1 of these drugs.[6] Effective doses of reserpine were 2-9 mg/d. Significant adverse effects were parkinsonism, dizziness, lethargy, depression, headache, GI upset, and hallucination. Effective doses of tetrabenazine were 12.5-250 mg/d. Most patients required >100 mg/d. Adverse effects include parkinsonism, depression, lethargy, euphoria, hallucinations, confusion, dizziness, vomiting, and unilateral leg tremor. Tetrabenazine (not available in United States) has minimal risk of tardive dyskinesia, which is an advantage compared to other antidopaminergic drugs.

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Tetrabenazine (Xenozine)

 

Presynaptic dopamine antagonist with minimal risk of tardive dystonia. Recently made available in United States, but very expensive.

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Atypical antipsychotics (serotonin dopamine receptor antagonists)

Class Summary

Atypical antipsychotics (eg, clozapine, risperidone, olanzapine) bind to dopamine D2 receptors and may improve tardive dystonia when lower doses are used. Recent trials have shown that they not only may cause or aggravate tardive dystonia but ultimately may prove to be highly useful therapeutic agents to treat dystonias. Long-term safety is not fully established for this indication.

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Clozapine (Clozaril)

 

Binds to dopamine D2 receptor with 20 times lower affinity than for serotonin-2 receptor.

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Anticholinergic agents

Class Summary

Anticholinergic therapy (eg, trihexyphenidyl, ethopropazine) has been used. Kang et al reported a 38% response to trihexyphenidyl alone and 44% when combined with other medications.[6] Effective doses were 10-32 mg/d. Severe adverse effects (eg, drowsiness, confusion, hallucinosis, memory difficulties) occurred at 60-100 mg/d. Ethopropazine showed 27% improvement when administered alone and 42% as adjuvant therapy. Doses were 100-450 mg/d. Adverse effects included confusion, forgetfulness, GI problems, dizziness, blurry vision, dry mouth, urinary retention, lethargy, palpitations, and sleep disturbances. Diphenhydramine, an anticholinergic with H1 antagonist properties, also has antidystonic effects.

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Trihexyphenidyl (Artane)

 

Central inhibitor of parasympathetic nervous system, resulting in diminished muscle spasms. Often DOC for young person with generalized, multifocal, or segmental dystonia, especially with lower extremities and trunk involvement.

Ethopropazine (Parsitan)

 

Not available in United States. Phenothiazine derivative that has antimuscarinic and antiparkinsonian activity. Demonstrates poor oral bioavailability.

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Acetylcholine receptor inhibitors

Class Summary

The most promising development for treating tardive dystonia and all other forms of dystonia has been botulinum toxin type A (BTTA). BTTA produces neuromuscular blockade by inhibiting the calcium ion–mediated release of acetylcholine at the motor nerve terminals. This results in diminished endplate potential and subsequent flaccid paralysis of the affected muscles. The paralysis persists until new nerve terminals form, usually within 2-3 months.

BTTA is effective in treating focal dystonias, including blepharospasm, oromandibular dystonia, spasmodic torticollis, spasmodic dysphonia (especially the adductor form), and some cases of focal limb dystonia. Injections are well tolerated. Systemic complications are not evident, although single-fiber electromyelogram studies show mild distant effects. Following administration, the onset of effect is apparent within a few days. Peak effects are evident within the first few weeks and wear off over 2-4 months.

Typical adverse effects are excessive weakness with inadvertent IM injection (eg, ptosis with eyelid injection, dysphagia in spasmodic torticollis). Treatment with large or frequent doses may prompt the development of antibodies to the toxin and may correlate with loss of the original benefit. Development of less antigenic forms of type A toxin or use of other botulinum toxin strains (ie, strains B or F) may overcome this problem. Patients should be advised that botulinum toxin is not curative but offers nonimmediate temporary improvement.

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OnabotulinumtoxinA (BOTOX®)

 

Neurotoxins produced by Clostridium botulinum exert paralytic effects at the neuromuscular junction by inhibiting the release of acetylcholine, thus, inhibiting impulse transmission in neuromuscular tissue. Has become a mainstay of therapy for focal and segmental dystonia, including tardive dystonia.

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Benzodiazepines

Class Summary

Bind to a specific benzodiazepine receptor on GABA receptor complex, thereby increasing GABA affinity for its receptor. Also increases the frequency of chlorine channel opening in response to GABA binding. GABA receptors are chlorine channels that mediate postsynaptic inhibition, resulting in postsynaptic neuron hyperpolarization. Final result is a sedative-hypnotic effect. Benzodiazepines may provide additional benefit. Clonazepam is effective for blepharospasm and myoclonic dystonia.

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Clonazepam (Klonopin)

 

Long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces monosynaptic and polysynaptic reflexes. Has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia).

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Contributor Information and Disclosures
Author

Daniel Schneider, MD  Movement Disorders Fellow, Center for Parkinson's Disease and Other Movement Disorders, Columbia University Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Paula D Ravin, MD  Associate Professor of Clinical Neurology, University of Massachusetts Memorial Health Care

Paula D Ravin, MD is a member of the following medical societies: American Academy of Neurology, American Headache Society, American Medical Association, Massachusetts Medical Society, and National Headache Foundation

Disclosure: Acadia Pharmaceuticals Grant/research funds Other; Bayer Pharmaceuticals Grant/research funds None; Teva Pharmaceuticals Grant/research funds Other

Specialty Editor Board

Alan D Schmetzer, MD  Professor Emeritus, Interim Chairman, Vice-Chair for Education, Associate Residency Training Director in General Psychiatry, Fellowship Training Director in Addiction Psychiatry, Department of Psychiatry, Indiana University School of Medicine; Addiction Psychiatrist, Midtown Mental Health Cener at Wishard Health Services

Alan D Schmetzer, MD is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Clinical Psychiatrists, American Academy of Psychiatry and the Law, American College of Physician Executives, American Medical Association, American Neuropsychiatric Association, American Psychiatric Association, and Association for Convulsive Therapy

Disclosure: Eli Lilly & Co. Grant/research funds Other

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Harold H Harsch, MD  Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin

Harold H Harsch, MD is a member of the following medical societies: American Psychiatric Association

Disclosure: lilly Honoraria Speaking and teaching; Forest Labs None None; Pfizer Grant/research funds Speaking and teaching; Northstar None None; Novartis Grant/research funds research; Pfizer Honoraria Speaking and teaching; Sunovion Speaking and teaching; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research; Merck Honoraria Speaking and teaching

Chief Editor

Iqbal Ahmed, MBBS, FRCPsych (UK)  Faculty, Department of Psychiatry, Tripler Army Medical Center; Clinical Professor of Psychiatry, Clinical Professor of Geriatric Medicine, University of Hawaii, John A Burns School of Medicine

Iqbal Ahmed, MBBS, FRCPsych (UK) is a member of the following medical societies: Academy of Psychosomatic Medicine, American Association for Geriatric Psychiatry, American Neuropsychiatric Association, American Psychiatric Association, American Society of Clinical Psychopharmacology, and Royal College of Psychiatrists

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Nestor Galvez-Jimenez, MD, and Perla Periut, MD, to the development and writing of this article.

References

  1. Fahn S, Marsden, CD, Calne DB. Classification and Investigation of Dystonia. In: Marsden CD, Fahn S. Movement Disorders, Vol. 2. London: Butterworths; 1987:332-358.

  2. Fahn, Stanley and Jankovic, Joseph. Principles and Practice of Movement Disorders. Philadelphia, PA: Churchill Livingston Elveiser; 2007.

  3. Stacy, Mark A. Handbook of Dystonia. New York, NY: Informa Healthcare; 2007.

  4. Keegan DL, Rajput AH. Drug induced dystonia tarda: treatment with L-dopa. Dis Nerv Syst. Mar 1973;34(3):167-9. [Medline].

  5. Burke RE, Fahn S, Jankovic J, et al. Tardive dystonia: late-onset and persistent dystonia caused by antipsychotic drugs. Neurology. Dec 1982;32(12):1335-46. [Medline].

  6. Kang UJ, Burke RE, Fahn S. Tardive dystonia. Adv Neurol. 1988;50:415-29. [Medline].

  7. Adityanjee, Aderibigbe YA, Jampala VC, Mathews T. The current status of tardive dystonia. Biol Psychiatry. Mar 15 1999;45(6):715-30. [Medline].

  8. Sachdev P. Risk factors for tardive dystonia: a case-control comparison with tardive dyskinesia. Acta Psychiatr Scand. Aug 1993;88(2):98-103. [Medline].

  9. Mihara K, Kondo T, Higuchi H, Takahashi H, Yoshida K, Shimizu T. Tardive dystonia and genetic polymorphisms of cytochrome P4502D6 and dopamine D2 and D3 receptors: a preliminary finding. Am J Med Genet. Aug 8 2002;114(6):693-5. [Medline].

  10. Trugman JM, Leadbetter R, Zalis ME, Burgdorf RO, Wooten GF. Treatment of severe axial tardive dystonia with clozapine: case report and hypothesis. Mov Disord. Jul 1994;9(4):441-6. [Medline].

  11. Yassa R, Nair V, Iskandar H. A comparison of severe tardive dystonia and severe tardive dyskinesia. Acta Psychiatr Scand. Aug 1989;80(2):155-9. [Medline].

  12. Friedman JH, Kucharski LT, Wagner RL. Tardive dystonia in a psychiatric hospital. J Neurol Neurosurg Psychiatry. Jun 1987;50(6):801-3. [Medline].

  13. Sethi KD, Hess DC, Harp RJ. Prevalence of dystonia in veterans on chronic antipsychotic therapy. Mov Disord. 1990;5(4):319-21. [Medline].

  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. Nov 1998;121 (Pt 11):2053-66. [Medline].

  15. Gimenez-Roldan S, Mateo D, Bartolome P. Tardive dystonia and severe tardive dyskinesia. A comparison of risk factors and prognosis. Acta Psychiatr Scand. May 1985;71(5):488-94. [Medline].

  16. Burke RE. Neuroleptic-induced tardive dyskinesia variants. In: Lang AE, Weiner WJ, eds. Drug-Induced Movement Disorders. New York, NY: Futu; 1992:168-98.

  17. Vandel P, Bonin B, Leveque E, et al. Tricyclic antidepressant-induced extrapyramidal side effects. Eur Neuropsychopharmacol. Aug 1997;7(3):207-12. [Medline].

  18. Gabellini AS, Pezzoli A, De Massis P, Sacquegna T. Veralipride-induced tardive dystonia in a patient with bipolar psychosis. Ital J Neurol Sci. Oct 1992;13(7):621-3. [Medline].

  19. Chakrabarti S, Chand PK. Lithium - induced tardive dystonia. Neurol India. Dec 2002;50(4):473-5. [Medline].

  20. Chase TN, Tamminga CA, Burrows H. Positron emission tomographic studies of regional cerebral glucose metabolism in idiopathic dystonia. Adv Neurol. 1988;50:237-41. [Medline].

  21. Arai N, Amano N, Iseki E, et al. Tardive dyskinesia with inflated neurons of the cerebellar dentate nucleus. Case reports and morphometric study. Acta Neuropathol (Berl). 1987;73(1):38-42. [Medline].

  22. Kaufman DM. Use of botulinum toxin injections for spasmodic torticollis of tardive dystonia. J Neuropsychiatry Clin Neurosci. Winter 1994;6(1):50-3. [Medline].

  23. Hennings JM, Krause E, Bötzel K, Wetter TC. Successful treatment of tardive lingual dystonia with botulinum toxin: case report and review of the literature. Prog Neuropsychopharmacol Biol Psychiatry. Jul 1 2008;32(5):1167-71. [Medline].

  24. Shapleske J, Mickay AP, Mckenna PJ. Successful treatment of tardive dystonia with clozapine and clonazepam. Br J Psychiatry. Apr 1996;168(4):516-8. [Medline].

  25. Blake LM, Marks RC, Nierman P, Luchins DJ. Clozapine and clonazepam in tardive dystonia. J Clin Psychopharmacol. Aug 1991;11(4):268-9. [Medline].

  26. Trottenberg T, Volkmann J, Deuschl G, Kühn AA, Schneider GH, Müller J. Treatment of severe tardive dystonia with pallidal deep brain stimulation. Neurology. Jan 25 2005;64(2):344-6. [Medline].

  27. Zhang JG, Zhang K, Wang ZC. Deep brain stimulation in the treatment of tardive dystonia. Chin Med J (Engl). May 5 2006;119(9):789-92. [Medline].

  28. Thobois S, Ballanger B, Xie-Brustolin J, Damier P, Durif F, Azulay JP, et al. Globus pallidus stimulation reduces frontal hyperactivity in tardive dystonia. J Cereb Blood Flow Metab. Jun 2008;28(6):1127-38. [Medline].

  29. Gruber D, Trottenberg T, Kivi A, Schoenecker T, Kopp UA, Hoffmann KT, et al. Long-term effects of pallidal deep brain stimulation in tardive dystonia. Neurology. Jul 7 2009;73(1):53-8. [Medline].

  30. Berg D, Becker G, Naumann M, Reiners K. Morphine in tardive and idiopathic dystonia (short communication). J Neural Transm. 2001;108(8-9):1035-41. [Medline].

  31. Burke RE, Kang UJ. Tardive dystonia: clinical aspects and treatment. In: Jankovic J, Tolosa E, eds. Facial Dyskinesias. New York, NY: Raven; 1988:200-10.

  32. Chatterjee A, Forrest Gordon M, Giladi N, Trosch R. Botulinum toxin in the treatment of tardive dystonia. J Clin Psychopharmacol. Dec 1997;17(6):497-8. [Medline].

  33. Eidelberg D, Moeller JR, Ishikawa T, et al. The metabolic topography of idiopathic torsion dystonia. Brain. Dec 1995;118 (Pt 6):1473-84. [Medline].

  34. Fahn S. Concept and classification of dystonia. Adv Neurol. 1988;50:1-8. [Medline].

  35. Franzini A, Marras C, Ferroli P, Zorzi G, Bugiani O, Romito L. Long-term high-frequency bilateral pallidal stimulation for neuroleptic-induced tardive dystonia. Report of two cases. J Neurosurg. Apr 2005;102(4):721-5. [Medline].

  36. Gruber D, Trottenberg T, Kivi A, Schoenecker T, Kopp UA, Hoffmann KT, et al. Long-term effects of pallidal deep brain stimulation in tardive dystonia. Neurology. Jul 7 2009;73(1):53-8. [Medline].

  37. Manteghi A, Hojjat SK, Javanbakht A. Remission of tardive dystonia with electroconvulsive therapy. J Clin Psychopharmacol. Jun 2009;29(3):314-5. [Medline].

  38. Reich SG. Dystonia. In: Johnson RT, Griffin JW, eds. Current Therapy in Neurologic Disease. St Louis, Mo: Mosby Year-Book; 1997:286-90.

  39. Simpson GM. The treatment of tardive dyskinesia and tardive dystonia. J Clin Psychiatry. 2000;61 Suppl 4:39-44. [Medline].

  40. Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management. CNS Drugs. 2002;16(3):165-74. [Medline].

  41. van Harten PN, Kahn RS. Tardive dystonia. Schizophr Bull. 1999;25(4):741-8. [Medline].

  42. van Harten PN, Matroos GE, Van Os J. The course of tardive dystonia in Afro Caribbean patients, a population-based study: the Curacao extrapyramidal syndromes study: VII. Schizophr Res. Jan 2008;98(1-3):79-83. [Medline].

 
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