||This article needs additional citations for verification. (January 2012)|
|Classification and external resources|
Tardive dyskinesia / / is a difficult-to-treat form of dyskinesia, a disorder resulting in involuntary, repetitive body movements. In this form of dyskinesia, the involuntary movements are tardive, meaning they have a slow or belated onset. This neurological disorder frequently appears after long-term or high-dose use of antipsychotic drugs,[N 1] or in children and infants as a side effect from usage of drugs for gastrointestinal disorders.[N 2]
Tardive dyskinesia is characterized by repetitive, involuntary, purposeless movements. Some examples of these types of involuntary movements include grimacing, tongue protrusion, lip smacking, puckering and pursing of the lips, and rapid eye blinking. Rapid, involuntary movements of the limbs, torso, and fingers may also occur. In some cases, an individual's legs can be so affected that walking becomes difficult or impossible. These symptoms are the opposite of patients who are diagnosed with Parkinson's disease. Parkinson's patients have difficulty moving, whereas tardive dyskinesia patients have difficulty not moving.
Respiratory irregularity, such as grunting and difficulty breathing, is another symptom associated with tardive dyskinesia, although studies have shown that the prevalence rate is relatively low.
Tardive dyskinesia is often misdiagnosed as a mental illness rather than a neurological disorder, and as a result patients are prescribed neuroleptic drugs, which enhance the probability that the patient will develop a severe and disabling case, and may even experience a shorter survival period.
Other closely related neurological disorders have been recognized as variants of tardive dyskinesia. Tardive dystonia is similar to standard dystonia but permanent. Tardive akathisia involves painful feelings of inner tension and anxiety and a compulsive drive to move the body. In some extreme cases, afflicted individuals experience so much internal torture that they lose their ability to sit still. Tardive tourettism is a tic disorder featuring the same symptoms as Tourette syndrome. The two disorders are extremely close in nature and oftentimes can only be differentiated by the details of their respective onsets. Tardive myoclonus, a rare disorder, presents as brief jerks of muscles in the face, neck, trunk, and extremities.
Tardive dyskinesia was first described in the 1950s shortly after the introduction of chlorpromazine and other antipsychotic drugs. However, the exact mechanism of the disorder remains largely uncertain. The most compelling line of evidence suggests that tardive dyskinesia may result primarily from neuroleptic-induced dopamine supersensitivity in the nigrostriatal pathway, with the D2 dopamine receptor being most affected. Neuroleptics act primarily on this dopamine system, and older neuroleptics, which have greater affinity for the D2 binding site, are associated with high risk for tardive dyskinesia. The D2 hypersensitivity hypothesis is also supported by evidence of a dose-response relationship, withdrawal effects, studies on D2 agonists and antagonists, animal studies, and genetic polymorphism research.
Given similar doses of the same neuroleptic, differences among individuals still exist in the likelihood of developing tardive dyskinesia. Such individual differences may be due to genetic polymorphisms, which code for D2 receptor binding site affinity, or prior exposure to environmental toxins. Decreased functional reserve or cognitive dysfunction, associated with aging, mental retardation, alcohol and drug abuse, or traumatic head injuries, has also been shown to increase risk of developing the disorder among those treated with neuroleptics. Antipsychotic drugs can sometimes camouflage the signs of tardive dyskinesia from occurring in the early stages; this can happen from the individual having an increased dose of an antipsychotic drug. Oftentimes the symptoms of tardive dyskinesia are not apparent until the individual comes off of the antipsychotic drugs; however, when tardive dyskinesia worsens, the signs become visible.
Other dopamine antagonists and antiemetics can cause tardive dyskinesia, such as metoclopramide and promethazine, used to treat gastrointestinal disorders. While newer atypical antipsychotics such as olanzapine and risperidone appear to have fewer dystonic effects, only clozapine has been shown to have a lower risk of tardive dyskinesia than older antipsychotics. There has been a reported case of the anti-psychotic medication aripiprazole, a partial agonist at D2 receptors, leading to tardive dyskinesia.
The available research seems to suggest that the concurrent prophylactic use of a neuroleptic and an antiparkinsonian drug is useless to avoid early extrapyramidal side-effects and may render the patient more sensitive to tardive dyskinesia. Since 1973 the use of these drugs has been found to be associated with the development of tardive dyskinesia.
Primary prevention of tardive dyskinesia is achieved by using the lowest effective dose of a neuroleptic for the shortest time. However, with diseases of chronic psychosis such as schizophrenia, this strategy must be balanced with the fact that increased dosages of neuroleptics are more beneficial in preventing recurrence of psychosis. If tardive dyskinesia is diagnosed, the causative drug should be discontinued. Tardive dyskinesia may persist after withdrawal of the drug for months, years or even permanently. Some studies suggest that physicians should consider using atypical antipsychotics as a substitute to typical antipsychotics for patients requiring medication. These agents are associated with fewer neuromotor side effects and a lower risk of developing tardive dyskinesia.
Currently, the only approved drug for treating tardive dyskinesia and other movement disorders is tetrabenazine, which is a dopamine depleting drug. Ondansetron (Zofran) has shown some benefit in experimental studies on tardive dyskinesia and a variety of anti-Parkinsonian medications are used such as Aricept, Baclofen, Requip and Mirapex. Clonidine is used for dystonic spasms and can be of help. Botox injections are used for minor focal dystonia, but not in more advanced tardive dyskinesia. A review paper found benzodiazepines[N 3] to be effective in alleviating the symptoms of tardive dyskinesia. However, like most anticonvulsants, benzodiazepines may cause tremors as well as benzodiazepine withdrawal syndrome upon rapid discontinuation.
In males, the branched-chain amino acid formula Tarvil, containing the amino acids valine, isoleucine, and leucine in a 3:3:4 ratio was reported as beneficial for motor symptoms in a small, non-blinded study.
In 1981, Charles Tkacz, M.D, and David R. Hawkins, M.D published the paper A Preventive Measure for Tardive Dyskinesia in the Journal of Orthomolecular Psychiatry/Medicine, detailing the clinical use of the vitamins Ascorbic Acid, either Niacinamide (Formula 1) / Niacin (Formula 2), Pyridoxine HC1, and d-AlphaTocopheryl Acetate in the prevention of Tardive Dyskenesia
Recent studies have tested the use of melatonin, high dosage vitamins, and different antioxidants in concurrence with antipsychotic drugs (often used to treat schizophrenia) as a way of preventing and treating tardive dyskinesia. Although further research is needed, studies reported a much lower percentage of individuals developing tardive dyskinesia than the current prevalence rate for those taking antipsychotic drugs.
Tardive dyskinesia most commonly occurs in patients with psychiatric conditions who are treated with antipsychotic medications for many years. The average prevalence rate has been estimated to be around 30% for individuals taking antipsychotic medication, such as that used to treat schizophrenia. A study being conducted at the Yale University School of Medicine has estimated that "32% of patients develop persistent tics after 5 years on major tranquilizers, 57% by 15 years, and 68% by 25 years." More drastic data was found during a longitudinal study conducted on individuals 45 years of age and older who were taking antipsychotic drugs. According to this research study, 26% of patients developed tardive dyskinesia after just one year on the medication. Another 60% of this at-risk group developed the disorder after 3 years, and 23% developed severe cases of tardive dyskinesia within 3 years. According to these estimates, the majority of patients will eventually develop the disorder if they remain on the drugs long enough.
Elderly patients are more prone to develop tardive dyskinesia, and elderly women are more at-risk than elderly men. The risk is much lower for younger men and women, and also more equal across the sexes. Patients who have undergone electro-convulsive therapy or have a history of diabetes or alcohol abuse also have a higher risk of developing tardive dyskinesia.
Several studies have recently been conducted comparing the prevalence rate of tardive dyskinesia with second generation, or more modern, antipsychotic drugs to that of first generation drugs. Some of these studies claim that the newer, second generation antipsychotic drugs have a reduced potential for causing tardive dyskinesia. Conversely, other studies dispute these claims and report that the prevalence rate has not significantly decreased with the use of more expensive antipsychotic medication.
A physician can evaluate and diagnose a patient with tardive dyskinesia by conducting a systematic examination. The physician should ask the patient to relax, and look for symptoms like facial grimacing, eye or lip movements, tics, respiratory irregularities, and tongue movements. In some cases, patients experience nutritional problems, so a physician can also look for a gain or loss in weight.
Tardive dyskinesia can be socially disabling, perhaps in addition to the underlying psychiatric disorder, and may cause inflicted patients to isolate themselves. Stressful events can also trigger the onset of dyskinetic movements, whereas relaxation and sedation reduce the severity of symptoms in patients.
- "tardive dyskinesia" at Dorland's Medical Dictionary
- Breggin, Peter. "Tardive Dyskinesia Legal Settlement".[unreliable medical source?]
- National Institutes of Health, National Institute of Neurological Disorders and Stroke. (2011). Ninds tardive dyskinesia information page. Retrieved from website: http://www.ninds.nih.gov/disorders/tardive/tardive.htm
- Nasrallah, H. (2003, Sept). Tardive dyskinesia. Retrieved from http://www.nami.org/Content/ContentGroups/Helpline1/Tardive_Dyskinesia.htm
- Duke University Health System. (2010, May 17). Additional movement disorders. Retrieved from http://www.dukehealth.org/services/neurological_disorders/care_guides/additional_movement_disorders/
- Yassa, R.; Lal, S. (1986). "Respiratory irregularity and tardive dyskinesia a prevalence study". Acta Psychiatrica Scandinavica 73 (5): 506–10. doi:10.1111/j.1600-0447.1986.tb02717.x. PMID 2875609.
- Yassa, Ramzy; Jones, Barry D. (1985). "Complications of tardive dyskinesia: A review". Psychosomatics 26 (4): 305–7, 310, 312–3. doi:10.1016/S0033-3182(85)72863-0. PMID 2859630.
- Dean, C. E.; Thuras, P. D. (2009). "Mortality and tardive dyskinesia: Long-term study using the US National Death Index". The British Journal of Psychiatry 194 (4): 360–4. doi:10.1192/bjp.bp.108.049395. PMID 19336789.
- Baldessarini, Ross J. (1988). "A summary of current knowledge of tardive dyskinesia". L'Encéphale 14 (Spec Issue): 263–8. PMID 2905654.
- Hoerger, Michael. "The primacy of neuroleptic-Induced D2 receptor hypersensitivity in tardive dyskinesia".[unreliable medical source?]
- Ross, Colin A; Read, John (2004). "Antipsychotic medication: myths and facts". In Read, John; Mosher, Loren R.; Bentall, Richard P. Models of Madness: Psychological, Social and Biological Approaches to Schizophrenia. London: Brunner-Routledge. pp. 101–14. ISBN 978-1-58391-906-4.
- Craig; Stitzel. Modern Pharmacology (6th ed.). p. 401.
- Abbasian, C; Power, P (2008). "A case of aripiprazole and tardive dyskinesia". Journal of Psychopharmacology 23 (2): 214–5. doi:10.1177/0269881108089591. PMID 18515468.
- Crane, GE (1973). "Is tardive dyskinesia a drug effect?". The American journal of psychiatry 130 (9): 1043–4. PMID 4727768.
- Crane, GE (1973). "Rapid reversal of tardive dyskinesia". The American journal of psychiatry 130 (10): 1159. PMID 4728916.
- Rauchverger, B; Isakov, V; Jabarin, M (2007). "Olanzapine-induced tardive dystonia successfully treated by tetrabenazine". The Journal of neuropsychiatry and clinical neurosciences 19 (4): 484–5. doi:10.1176/appi.neuropsych.19.4.484-a. PMID 18070868.
- Fernandez, Hubert H.; Friedman, Joseph H. (2003). "Classification and Treatment of Tardive Syndromes". The Neurologist 9 (1): 16–27. doi:10.1097/01.nrl.0000038585.58012.97. PMID 12801428.
- Saltz, Bruce L.; Robinson, Delbert G.; Woerner, Margaret G. (2004). "Recognizing and Managing Antipsychotic Drug Treatment Side Effects in the Elderly". Primary Care Companion to the Journal of Clinical Psychiatry 6 (Suppl 2): 14–9. PMC 487007. PMID 16001096.
- Brasic, James Robert (February 9, 2012). "Tardive Dyskinesia". In Benbadis, Selim R. eMedicine.
- Bhoopathi, Paranthaman Sethupathi; Soares-Weiser, Karla (2006). "Benzodiazepines for neuroleptic-induced tardive dyskinesia". In Bhoopathi, Paranthaman Sethupathi. Cochrane Database of Systematic Reviews (3): CD000205. doi:10.1002/14651858.CD000205.pub2. PMID 16855954.
- Richardson, Mary Ann; Bevans, Margaret L.; Read, Laura L.; Chao, Helen M.; Clelland, James D.; Suckow, Raymond F.; Maher, Timothy J.; Citrome, Leslie (2003). "Efficacy of the Branched-Chain Amino Acids in the Treatment of Tardive Dyskinesia in Men". American Journal of Psychiatry 160 (6): 1117–24. doi:10.1176/appi.ajp.160.6.1117. PMID 12777270.
- Tkacz, Charles; Hawkins, David R. (1981). "A Preventive Measure for Tardive Dyskinesia". Journal of Orthomolecular Psychiatry.
- Lerner, Vladimir (2011). "Antioxidants as a Treatment and Prevention of Tardive Dyskinesia". Handbook of Schizophrenia Spectrum Disorders, Volume III. pp. 109–34. doi:10.1007/978-94-007-0834-1_6. ISBN 978-94-007-0833-4.
- Llorca, Pierre-Michel; Chereau, Isabelle; Bayle, Frank-Jean; Lancon, Christophe (2002). "Tardive dyskinesias and antipsychotics: A review". European Psychiatry 17 (3): 129–38. doi:10.1016/S0924-9338(02)00647-8. PMID 12052573.
- Glenmullen, Joseph (2001). Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants With Safe, Effective Alternatives. New York: Simon & Schuster. p. 38. ISBN 978-0-7432-0062-2.[unreliable medical source?] ::referring to Glazer, William M.; Morgenstern, Hal; Doucette, John T. (1993). "Predicting the long-term risk of tardive dyskinesia in outpatients maintained on neuroleptic medications". Journal of Clinical Psychiatry 54 (4): 133–9. PMID 8098030.
- Jeste, Dilip V.; Caligiuri, Michael P.; Paulsen, Jane S.; Heaton, Robert K.; Lacro, Jonathan P.; Harris, M. Jackuelyn; Bailey, Anne; Fell, Robert L. et al. (1995). "Risk of Tardive Dyskinesia in Older Patients: A Prospective Longitudinal Study of 266 Outpatients". Archives of General Psychiatry 52 (9): 756–65. doi:10.1001/archpsyc.1995.03950210050010. PMID 7654127.
- Whitaker, Robert (2002). Mad in America: Bad Science, Bad Medicine, and the Enduring Mistreatment of the Mentally Ill. Perseus.[page needed]
- Marshall, DL; Hazlet, TK; Gardner, JS; Blough, DK (2002). "Neuroleptic drug exposure and incidence of tardive dyskinesia: A records-based case-control study". Journal of managed care pharmacy 8 (4): 259–65. PMID 14613418.
- Tarsy, Daniel; Lungu, Codrin; Baldessarini, Ross J. (2011). "Epidemiology of tardive dyskinesia before and during the era of modern antipsychotic drugs". In Vinken, P. J.; Bruyn, G. W. Handbook of Clinical Neurology. Hyperkinetic Movement Disorders 100. pp. 601–16. doi:10.1016/B978-0-444-52014-2.00043-4. ISBN 978-0-444-52014-2. PMID 21496610.
- Jeste, Dilip V.; Caligiuri, Michael P. (1993). "Tardive Dyskinesia". Schizophrenia Bulletin 19 (2): 303–15. doi:10.1093/schbul/19.2.303. PMID 8100643.