|This section contains scientific literature on tardive dyskinesia (TD)|
(1) TD rates in adults are very high. Note the “authoritative” sources that confirm high rates, including the American Psychiatric Association (see documents labelled APA). Overall, estimates of TD rates in individuals 18-54 are in the range of 5-8% per year, accumulating year after year. This is an extremely high risk for a potentially disabling, disfiguring and torturous disorder. The rates for the elderly are many times higher (see II. 6).
- APA 1985, member letter TD
- APA 1999, text book of psychiatry (TD) 3rd edition
- APA 2000, DSM-IV-TR
- APA 1994, DSM-IV
- Archives 1973, neurological syndromes with antipsychotics
- Asnis 1977, survey of TD in psychiatric outpatients
- Chouinard 1979, factors related to TD
- Chouinard 1986, 5-year follow up study TD
- Chouinard 1988, 5-yr prospective study of TD new cases
- Glazer 1993, predicting long-term risk TD in neuroleptic patients
- Jeste 1981, changing epidemiology of TD
- Kane 1980, prevalence of presumed TD in- & out-patients
- Kiriakakis 1998, dystonia longterm
- Morgenstern 1993, risk factors for TD, long-term outpatients
- Mukherjee 1982, TD in psychiatric outpatients
- Smith 1979, assessment of TD in schizophrenics
- Tepper 1979, prevalence of TD
- Woods 2010, atypicals and high rates of TD
- Yassa 1995, prevalence of TD in fluphenazine patients
(2) TD rates in the elderly are astronomical. Tardive dyskinesia in the elderly is one of the worst medical catastrophes. In controlled clinical trials, rates for the elderly for TD exceed 20% per year, and accumulate year after year. In addition to the Black Box Warnings about increase mortality in elderly patients for all antipsychotic drugs, the risk to patients is enormously greater than any possible benefit. I do not know of any studies of TD in elderly from the newer antipsychotics; the drug companies are avoiding the issue. However, as documented above (II. 2), TD rates are not substantially different among various antipsychotic drugs. Indeed, the FDA requires a similar class warning for TD for all antipsychotic drugs. Keep in mind that “elderly” often includes people as young as age 55. I have included an incomplete very brief summary of the results of a number of scientific reports for TD rates in the elderly and all the original studies are included in the folder.
- APA DSM-IV-TR (2000) 4th ed TR
- Breggin Summary Data from TD Elderly Reports
- Caligirui, M., etal (1997) incidence-risk factors for severe TD in older pat.
- Jeste, D, TD in older patients (2000)
- Jeste, D., etal (1995) risk of TD in older patients
- Jeste, D., etal (1999) incidence of TD early stages,low dose neurolept.
- Jeste, D., etal 1993 trtmnt of late life schizophrenia
- Paulsen, J., etal (1996) risk factors for orofacial limbtruncal TD
- Saltz, B., (1989) prospective study of TD in elderly
- Saltz, B., etal 1991 prospective study td incidence-elderly
- Woerner, M., etal (1998) prospective study of TD in elderly
- Yassa, etal, 1988 TD biological mechanisms and clin. apects
- Yassa, R., etal (1992) TD in elderly a 5yr study
(3) TD rates in children are similar or higher than in adults. In one of my earliest medical books (P. Breggin, Psychiatric Drugs: Hazards to the Brain, Springer, 1983), I marshaled evidence for the first time about the high risk of tardive dyskinesia in children. Since then, “authorities” routinely admit that it is risk, but too many negligent prescribers act as if it is not.
- APA (1992) Task Force guidline
- Connor (2001) TD Atypicals Children
- Gualtieri (1988) Tardive Dyskinesia
- Gualtieri (2002) Tardive Dyskinesia
(4) Permanent brain damage and dysfunction, including cognitive dysfunction, dementia, tardive psychosis, and atrophy (shrinkage) of brain tissue with cell death caused by antipsychotic drugs. Brain atrophy can occur early in treatment even before TD develops. I was among the first to warn about the risk of antipsychotic drug-induced dementia and atrophy of the brain in my 1983 book, Psychiatric Drugs, and I have continued to document this risk in my most recent textbooks, Brain-Disabling Treatments in Psychiatry (2008) and Psychiatric Drug Withdrawal (2013). These drastic, tragic outcomes are the result of the extreme neurotoxicity of the antipsychotic drugs.
- Arango, C. et al atrophy children schizphrenia antipsychotics
- Breggin 2011 chronic brain impairment
- Breggin 1990 brain damage.and dementia
- Breggin 1993 antipsychotric drugs and lethargic encephalitis
- Breggin additional notes on antipsychotic brain damage
- Breggin notes on earlier studies
- Dorph-Petersen 2005 monkey brain damage
- Gualtieri 2002 highlighted tardive dyskinesia akathasia
- Gualtieri 1988 tardive dyskinesia
- Ho atrophy 2011
- Khorram 2006 atrophy of brain
- King 1994 psychomotor impairment
- Konopaske 2007 shrinkage, cell death, atrophy animals
- Lewis 2009 atrophy comments on Navari conflicts of interest
- Lewis 2011 antipsychotic meds & brain volume atrophy editorial
- Navari & Dazzan 2009 brain damage atrophy review
- vanHaren 2011 brain atrophy, brain scans, schizophrenia
- Vita 2015 antipsychotic brain damage
- Wolf 1983 cognitive dysfunction dementia TD
(5) Standards of care for preventing TD in children, adults and the elderly are well-documented. Here are a few psychiatric sources that are particular useful from the American Psychiatric Association. Of special interest are three publications from the American Geriatric Society (AGS) concerning the Beers Criteria for medication use in the elderly, which make clear that antipsychotic drugs should be “avoided” in treating the elderly. This folder contains a Beers Criteria article from 2012 and 2015. A second 2012 article intended for the public provides an excellent summary.
- AGS (2012) Beers Criteria Simplified for Elderly & Drugs
- AGS (2012) Scientific paper on medications for elderly
- AGS (2015). Beers Criteria Elderly and Medication
- APA (1985). Letter warning about TD to association membership.
- APA (1992) Task Force guidline
- APA (1999) Textbook of Psychiatry (TD) & later editions
- Haag Who recommended documentation
(6) Dr. Peter Breggin’s work. The best sources of my current research on these subjects are in two of my more recent books, Psychiatric Drug Withdrawal (2013) and Brain-Disabling Treatments in Psychiatry, Second Edition (2008). I am also including a few of my articles that deal with antipsychotic drug adverse effects, including tardive dyskinesia, tardive psychosis and tardive dementia.
- Breggin 1990 Brain damage and dementia
- Breggin 1993 Antipsychotics & lethargic encephalitis
- Breggin 2008 Brain-Disabling Treatments in Psychiatry, Second Edition
- Breggin 2011 Chronic Brain Impairment
- Breggin 2013 Psychiatric Drug Withdrawal
- Breggin 2016 Rational Principles of Psychopharmacology
(7) Scientific studies confirm that “atypical” antipsychotic drugs cause typical extrapyramidal reactions (EPS) and TD. In addition to the scientific studies, Full Prescribing Information are provided for Risperdal, Abilify and Saphris to show that they block dopamine type 2 neurons and that they are considered to cause TD by the FDA. Indeed, all so-called atypicals are dopamine blockers and therefore they cause TD. For example, J&J (Johnson & Johnson), their medical consultants, and scientifically alert prescribers from the beginning should have known that Risperdal (as well as other so-called atypicals) would cause tardive dyskinesia at a high rate. From the beginning, the FDA-approved Risperdal label or Full Prescribing Information stated that Risperdal was an “antagonist” (blocker) with “high affinity” for “Dopamine Type 2 (D2).” That is, Risperdal is a potent blocker of D2 neurons and therefore would inevitably cause TD. Similarly, Abilify’s label states that the drug “exhibits high affinity for dopamine D2…” A new drug Saphris has similar observations and all three have warnings about TD. In addition to the studies cited in this group, see group (8) below with more than two dozen reports of tardive dyskinesia caused by Risperdal published prior to 1985.
- Abilify 2011 Full Prescribing Informaiton
- Abilify 2014 Full Prescribing Info
- Chouinard 2008 Atypicals CATIE
- Kapur 1999 Clinical implications of dopamine blockade
- Lieberman and Stroup 2011, Emperor’s new clothes, CATIE study results
- Lieberman CATIE 2005 effectiveness & adverse effects
- Miller 2008 TD & EPS Atypicals
- Risperdal 2003 Full Prescribing Information highlights
- Risperdal 2014 Full Prescribing Information
- Rosebush 1999, Risperdal is not atypical. Causes EPS in PD.
- Saphris 2015 Full Prescribing Information
- Woods 2010 TD atypicals
(8) Reports of Risperdal-induced TD published prior to 2005. One of the false claims made the defense in lawsuits pertaining to Risperdal and TD, as well as to other “atypical” antipsychotic drugs, is that there was no way for the drug company, its consultants, or prescribers to know early on that so-called atypicals would cause TD. The section contains nearly two dozen clinical reports of Risperdal tardive dyskinesia published before 2005, including a few involving children.
- 1995 Risperdal TD Addington
- 1996 Risperdal TD Anand
- 1996 Risperdal TD Buzan
- 1996 Risperdal TD child 18 Daniel
- 1996 Risperdal TD child Feeney
- 1996 Risperdal TD Review Umbrlcht
- 1996 Risperdal TD Woerner
- 1997 Risperdal TD Gwin
- 1997 Risperdal TD Haberfellner
- 1998 Risperdal TD Dubbelman abstract
- 1998 Risperdal TD Sakkas
- 1998 Risperdal TD Saran
- 1998 Risperdal TD Silberbauer
- 1999 Risperdal TD 2 cases Lykouras
- 1999 Risperdal TD 4x Campbell
- 1999 Risperdal TD Vercueil
- 2000 Risperdal TD Child Kumar
- 2001 Risperdal TD Ipekci
- 2001 Risperdal TD Morgensternre view
- 2002 Risperdal TD Vasudevan
- 2004 Risperdal TD Adamou
- 2004 Risperdal TD Kwon child
(9) James McCracken recently testified for the defense in a malpractice case involving tardive dyskinesia in a child. The case, in which I was an expert for the plaintiffs, was settled in trial shortly before I was scheduled to testify. Here are scientific articles jointly authored by McCracken favoring Risperdal for children with autism. These articles also mention some of his affiliations with drug companies; other times he avoids listing them. Check with Dr. Breggin for more information in this regard.
- Aman 2005, McCracken Safety of Risperdal in Autism
- Arnold, McCracken 2010, J & J Risperdal children
- McCracken 2002, Used for FDA Risperdal for autism children
- McCracken 2006, consultant to Janssen (J&J)
(10) Antipsychotic drugs especially damage the basal ganglia where the dopamine neurons originate. Tardive dyskinesia results from the permanent hypersensitivity and proliferation of these neurons as a compensatory reaction to the suppression and dysfunction caused by the antipsychotic drugs. A rudimentary knowledge of the function of the basal ganglia informs us that the dopaminergic nerves in the basal ganglia provide a main nerve trunk into the frontal lobes, as well as affecting the temporal lobes and other regions of the brain involved with memory, cognition, and all the higher human functions. It is no surprise, therefore, that tardive dyskinesia, a manifestation of damage to dopaminergic neurons, also causes cognitive deficits and even dementia. Here are a few of many scientific studies of the complex functions of the basal ganglia and the dopaminergic neurons that originate in them.
- Frank 2001 basal ganglia. cognitive emotinoal
- Leisman 2014 basal ganglia cognitive emotional functioning TD
- Leisman 2014 basal ganglia TD cognitive functioning
- Risperdal Liddle 2000 effects of basal ganglia
- Robinson 2008. Basal Ganglia Learning Memory
(11) Physicians too often fail to recognize or document TD. Neurologists, who often depend on psychiatrists for referrals, will often go to extremes to avoid actually diagnosing a patient with TD. I have seen cases in which everything in the patient’s history and clinical findings indicate TD but the consultant psychiatrist or neurologist refuses to make the specific diagnosis. Here are two articles about non-recognition of TD within psychiatry.
(12) Criminal and civil fines imposed on J&J (and subsidiary Janssen) for false marketing of Risperdal, leading to massive off-label, negligent use for children and the elderly, and all age ranges in general.
- J&J Has A New Image Campaign, But Some Things Don’t Change
- NYT describes $2.2 billion settlement
- Risperdal Texas v Janssen Complaint T-Map Allogorhythm
- Rothman Expert Report Texas v J&J Risperdal
- United States’ Civil Complaint
- U.S. Dept of Justice, Johnson & Johnson case documents
Psychiatric drugs are not only dangerous to take, they are also dangerous to withdraw from. Withdrawal from psychiatric drugs, including antipsychotic drugs, should be done cautiously with professional supervision.Please see my book, Peter R. Breggin, MD, Psychiatric Drug Withdrawal: A Guide for Prescribers, Therapists, Patients and their Families.