Tardive Dyskinesia

BACKGROUND

Description

Tardive dyskinesia (TD) is a neurological syndrome associated with long-term use of antipsychotic (neuroleptic) drugs prescribed to treat psychiatric disorders, particularly schizophrenia, as well as some gastrointestinal or neurological conditions. It is characterized by involuntary, purposeless movements—often choreiform (rapid, jerky, nonrepetitive), athetoid (slow, sinuous, continual), or rhythmic (stereotyped). TD usually involves muscles of the mouth and face, although any muscle in the body can be affected. Many cases of tardive dyskinesia are mild and TD does not always progress in severity, though some people develop severe and disabling TD. The dyskinetic movements are permanent in about half of people who develop them, they and are diminished by action of the involved body part and may be increased by the action of unaffected body parts. Psychological stresses, including excitement and agitation, have been shown to increase dyskinetic movements, while relaxation and sedation reduce the severity.

Characteristic movements include

Grimacing
Tongue protrusion
Smacking, sucking and licking of the lips
Puckering and pursing of the mouth
Rapid eye blinking
Foot tapping
Flexing of ankles
Hand clenching
Rocking
Swaying
Abnormal movements of the arms and legs (chorea and athetosis)

Tardive dyskinesia usually appears late in the course of drug therapy. For many people with TD, symptoms can decrease or disappear with a decrease or discontinuation of the medication, although in some people symptoms may continue indefinitely. In addition, symptoms may not be observed until the antipsychotic medication is decreased or withdrawn, since tardive dyskinesia may be masked by the drug that has caused the disorder. Reports have associated TD with older neuroleptics, including haloperidol (Haldol), thiothixene (Navane), fluphenazine (Prolixin), chlorpromazine (Thorazine) ((Edelson)), thioridazine (Mellaril), and trifluoperazine (Stelazine).

Causes

Long-term use of a neuroleptic drug (3 months up to years), which causes up-regulation of dopamine receptors
Metoclopramide, a D2-receptor blocker commonly used in nonpsychiatric medical patients (less common)

Although supersensitivity of striatal dopamine (DA) receptors was previously thought to result in the development of TD, it now seems that several neurotransmitter systems may be affected. These include dopaminergic, noradrenergic, gamma-amino-butyric acid (GABA)ergic, cholinergic, and peptidergic pathways.

Incidence

Overall mean prevalence of TD among individuals on chronic neuroleptic-treatment is approximately 24%.
The average yearly rate of developing TD is about 5% per year for the first several years.
The cumulative 5-year incidence rate appears to be 20-26%.
Rates are less clear, but assumed significantly lower, for atypical antipsychotics compared to older
antipsychotics.
Studies have not yet determined whether the risk levels off after 5 years or continues to increase.
People over age 40 are three times as likely to develop the disorder as those under 40.

Risk Factors

Older age
Length of neuroleptic treatment
Psychiatric diagnosis (people with mood disorders have increased risk)
Diabetes
Organic brain damage
Negative symptoms (in people with schizophrenia), i.e., poverty of speech or poverty of thought content,
anhedonia, flat affect (lack of emotional expression), loss of motivation (avolition), attentional, apathy, and
social withdrawal
Greater number of medication-free periods, “drug holidays”
History of acute extrapyramidal side effects (EPS), side effects involving nerves and muscles that result in
disturbance of voluntary motor function, in response to medication

Prerequisites to Diagnosis

At least 3 months of total neuroleptic exposure, including amoxapine and metoclopramide
At least moderate abnormal involuntary movements in one or more body areas or mild movements in two or more body
areas
The absence of other conditions that produce involuntary hyperkinetic dyskinesias

MEDICAL MANAGEMENT CONSIDERATIONS

There is no standard treatment for tardive dyskinesia. Providers work with the individual and his or her family to create a plan unique to the individual that best addresses his or her needs. Routine monitoring is important to track changes and progress. In general, prevention is key—people at-risk should be assessed at frequent intervals for early signs of TD.

Initial Evaluation

Conduct medical evaluation, including physical and neurological examinations, laboratory testing, and a review
of the differential diagnosis of movement disorders.

Prevention

Inform people on antipsychotic drugs of the risk of tardive dyskinesia.
Risks and benefits should be carefully weighed and delineated to the person when prescribing either long-term
neuroleptics or alternate medications used for their possibility of reducing chance of TD.
Restrict necessary neuroleptic drugs to well-defined indications; use them in the lowest effective doses.
Consider using an atypical antipsychotic, rather than a typical antipsychotic, that may have a reduced chance of
causing TD.
Perform exam every three months on people at risk for developing TD.
Preventive treatment with vitamin E or lithium has been suggested to reduce the incidence of tardive dyskinesia;
more studies are needed in support.

Treatment Considerations

Reevaluate need for antipsychotics; use other classes of medications or discontinue antipsychotic use when
possible. Keep prescription doses as low as possible to effectively control symptoms. (Note: discontinuance may
not necessarily lead to a disappearance or decrease in severity of tardive dyskinesia)
Consider using an atypical antipsychotic, rather than a typical antipsychotic, which may have a reduced chance
of causing TD.
Consider additional medications to suppress TD if the symptoms pose health risks or impair function.
Consider consultation with a psychiatrist when prescribing psychotropic medications.
Consider consultation with an occupational or physical therapist.

As of yet, there is no consistently beneficial pharmacologic therapy for TD, in spite of investigations of many drugs aimed at the dopaminergic, cholinergic, and GABAergic systems. New, atypical antipsychotics, including risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), sertindole (Serlect, Serdolect), ziprasidone (Geodon, Zeldox), and aripiprazole (Abilify, Abilitat), have been designed for use in place of older TD-causing antipsychotic drugs. It is yet to be determined clearly in clinical studies whether the long-term use of these atypical antipsychotics will lead to a lower incidence of tardive dyskinesia—risperidone has actually been associated with TD in some cases. Clozapine (Clozaril), an atypical antipsychotic agent rarely associated with tardive dyskinesia, was the first atypical antipsychotic to be used in place of TD-causing neuroleptics. Nonetheless, its use has been limited by a variety of other side effects, including agranulocytosis and the consequent need for a weekly monitoring of white blood cell counts, sedation, and seizures.

Medications with relatively few side effects that may suppress TD include calcium channel blockers (such as nifedipine), adrenergic antagonists, and vitamin E. Although vitamin E has not been proven definitively effective, it is commonly used and of minimal risk of toxicity. Treatment with the presynaptic dopamine depleters tetrabenazine (not available in the United States) and reserpine has met with fair success, but side effects have limited their use and the studies so far are of short duration. GABA agonists such as baclofen, valproic acid, or clonazepam may decrease hyperkinetic movements, but more studies are needed to support this conjecture.

Research is constantly underway in both the treatment and prevention of tardive dyskinesia, so physicians should conduct a thorough review of the most current studies and consider consulting a psychiatrist prior to prescribing treatment medications.

Management

Inform and involve both individuals with tardive dyskinesia and their family/caregivers in management so that
informed decisions can be made and documented.
Routinely monitor TD to track changes and response to medications every 4 to 6 months in people with TD, and
more often when medication changes are made. Scales by which to monitor include
- Abnormal Involuntary Movement Scale (AIMS), a common rating procedure examination
- Dyskinesia Identification System: Condensed User Scale (DISCUS), a standardized measure of TD for people
  with mental retardation

REFERENCES

Peer-Reviewed Journal Articles

Cummings, J.L., Wirshing, W.C. (1989). Recognition and differential diagnosis of tardive dyskinesia. The
International Journal of Psychiatry in Medicine, 19(2), 133-144.

Egan, M.F., Apud, J., Wyatt, R.J. (1997). Treatment of Tardive Dyskinesia. Schizophrenia Bulletin,
23(4), 583-609.

Jeste, D.V., Caligiuri, M.P. (1993). Tardive dyskinesia. Schizophrenia Bulletin, 19(2), 303-315.

Jeste, D.V., & Wyatt, R. J. (1985). Prevention and management of tardive dyskinesia. The Journal of Clinical
Psychiatry, 46(4), 14-18.

Kang, U.J., & Fahn, S. (1988). Management of Tardive Dyskinesia. Rational Drug Therapy, 22(8), 1-7.

The Management of Tardive Dyskinesia. (1986). Drug and Therapeutics Bulletin, 24(7), 27-28.

Matson, J.L., Mayville, E.A., Bielecki, J., Smalls, Y., Eckholdt,. C.S. (2002). Tardive Dyskinesia Associated with Metoclopramide in Persons with Developmental Disabilities [Abstract].
Research in Developmental Disabilities, 23(3), 224-233.

Other Publications

Brasic, J. R., & Bronson, B. (2003). Tardive Dyskinesia. Retrieved on June 15, 2006, from http://www.emedicine.com/neuro/topic362.htm

Dambro, M.R. (Ed.). (1999). Tardive Dyskinesia. In Griffith’s 5 Minute Clinical Consult (p. 1227)
. Baltimore: Lippincott Williams & Wilkins.

Edelson, S.M. (1995). Tardive Dyskinesia. Retrieved on June 15, 2006 from http://www.autism.org/tardiv.html

National Alliance for the Mentally Ill (NAMI). (2003). Tardive Dyskinesia
(TD). Retrieved on June 15, 2006, from http://www.nami.org/Content/ContentGroups/Helpline1/Tardive_Dyskinesia.htm

National Institute of Neurological Disorders and Stroke (NINDS). (2001). NINDS Tardive Dyskinesia Information
Page. Retrieved on June 15, 2006, from http://www.ninds.nih.gov/health_and_medical/disorders/tardive_doc.htm

National Organization for Rare Disorders (NORD). (1999). Tardive Dyskinesia. Retrieved on June 15, 2006, from http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Tardive%20Dyskinesia

Reber, M., Borcherding, B.G. (1997). Dual Diagnosis: Mental Retardation and Psychiatric Disorders. In M. L. Batshaw (Ed.),
Children with Disabilities (4^th ed., pp. 405-424). Baltimore: Paul H. Brookes.

Wickman, J.M., Cold, J. (2000). Recognizing and treating tardive dyskinesia. U.S. Pharmacist, 25(5)
. Retrieved on June 15, 2006, from http://www.uspharmacist.com/oldformat.asp?url=newlook/files/feat/may00tar.htm

RESOURCES FOR FAMILIES

The American Academy of Child and Adolescent Psychiatry

Phone: (202) 966-7300

http://www.aacap.org

American Academy of Neurology

Phone: (651) 695-2717

Phone: (800) 879-1960

E-mail: [email protected]

http://www.aan.com

Bazelon Center for Mental Health Law

Phone: (202) 467-5730

TTY: (202) 467-4232

E-mail: [email protected]

http://www.bazelon.org

California Alliance for the Mentally Ill

Phone: (916) 567-0163

Phone: (800) 950-NAMI

E-mail: [email protected]

http://namicalifornia.org

The Movement Disorder Society

Phone: (414) 276-2145

E-mail: [email protected]

http://www.movementdisorders.org

National Alliance for the Mentally Ill (NAMI)

Phone: (703) 524-7600

TTY: (703) 516-7227

NAMI HelpLine: (800) 950-NAMI (6264)

E-mail: [email protected]

http://www.nami.org

National Information Center for Children and Youth with Disabilities (NICHCY)

Voice/TTY: (800) 695-0285

E-mail: [email protected]

http://www.nichcy.org

National Institute of Mental Health (NIMH)

Tel: (301) 443-4513

TTY: (301) 443-8431

E-mail: [email protected]

http://www.nimh.nih.gov

NIH/National Institute of Neurological Disorders and Stroke (NINDS)
Brain Resources and Information Network (BRAIN)
Phone: (301) 496-5751

Phone: (800) 352-9424

http://www.ninds.nih.gov

National Mental Health Association
Phone: (703) 684-7722

TTY: (800) 433-5959

Phone: (800) 969-NMHA (6642)

E-mail: [email protected]

http://www.nmha.org

National Organization for Rare Disorders (NORD)

Phone: (203) 744-0100

Voice mail: (800) 999-NORD (6673)

TTY: (203) 797-9590

E-mail: [email protected]

http://www.rarediseases.org

The Resource Foundation for Children with Challenges

Special Child: for Parents and Caregivers of Children with Special Needs http://www.specialchild.com/index.html

Tardive Dyskinesia/Tardive Dystonia National Association

Phone: (206) 522-3166

E-mail: [email protected]

The Tarjan Center for Developmental Disabilities at UCLA

http://www.tarjancenter.ucla.edu

WE MOVE (Worldwide Education and Awareness for Movement Disorders)

Mt. Sinai Medical Center

Phone: (212) 241-8567

Phone: (800) 437-6682

E-mail: [email protected]

http://www.wemove.org

ADVISORY COMMITTEE

Robin L. Hansen, M.D.

Romie H. Holland, M.D.

Theodore A. Kastner, M.D., M.S.

Patrick J. Maher, M.D.

Felice Weber Parisi, M.D., M.P.H.

PUBLICATION INFORMATION

Funded by a grant from the California Department of Developmental Services

For more information, contact:

Center for Health Improvement

1330 21st Street, Suite 100

Sacramento, CA 95814

(916) 901-9645

This document does not provide advice regarding medical diagnosis or treatment for any individual case, and any opinions or statements contained in this document are not intended to serve as a standard of medical care. Physicians are encouraged to view the considerations presented in this document in light of evolving scientific information. This document is not intended for use by the layperson. Reproduction of this document may be done with proper credit given to the California Department of Developmental Services and the Center for Health Improvement.