|This section contains scientific literature on tardive dyskinesia (TD)|
Table of Contents
- TD rates among healthy young adults on antipsychotics
- TD rates among older adults on antipsychotics
- TD rates among children on antipsychotics
- New “atypicals” harmful as old antipsychotics
- Tardive psychosis and brain damage from antipsychotics
- Antipsychotics damage the basal ganglia
- Tardive Dystonia
- Tardive Akathisia
- Neuroleptic Malignant Syndrome (NMS)
- Early reports of Risperdal-induced TD
- James McCracken, defender of child TD
- Case against Johnson & Johnson
- Standards of care for preventing TD
- Physicians often fail to recognize TD
- Dr. Peter Breggin’s TD work.
(1) Tardive dyskinesia (TD) rates in adults are very high. Note the “authoritative” sources that confirm high rates, including the American Psychiatric Association (see documents labelled APA). TD occurs in young adults up to age 40 at a rate of at least 5–8% per year, accumulating with a risk of 20%–24% after four years (American Psychiatric Association, 1992, pp. 67-8; Chouinard et al., 1988 for the higher rate; Wojcieszek, 1998). TD annual rates rise steeply for middle-aged people: “For a 40-year-old patient, the risk is 18% at 2 years [9% per year] and 30% at 4 years” (Wojcieszek, 1998, p. 220). In patients older than age 45 years, “the cumulative incident of TD after neuroleptic exposure is 26%, 52%, and 60% after 1, 2, and 3 years, respectively (Wojcieszek, 1998, p. 220).
- APA 2000, DSM-IV-TR
- APA 1994, DSM-IV
- APA 1999, Text book of psychiatry (TD) 3rd edition
- APA 1992, TD Task Force
- APA 1985, Member letter TD
- 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
- Crawford 2008, TD in children
- 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
- Wojcieszek 1998
- 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. Numerous studies confirm even more tragically high rates of TD in people 55 and older: 41% in 24 months (Yassa et al., 1988); 35% in 20.7 months (Yassa et al., 1992); and 26% in 12 months (Jeste et al., 1993). The elderly may develop tardive dyskinesia after 2 weeks exposure (Saltz et al., 1991) and probably after a day or two in my clinical experience.
- APA DSM-IV-TR 2000, 4th Ed TR
- Breggin Summary Data from TD Elderly Reports
- Caligirui 1997, incidence-risk factors for severe TD in older pat.
- Jeste 2000, TD in older patients
- Jeste 1995, Risk of TD in older patients
- Jeste 1999, Incidence of TD early stages,low dose neurolept.
- Jeste 1993, Treatment of late life schizophrenia
- Paulsen 1996, Risk factors for orofacial limbtruncal TD
- Saltz 1989, Prospective study of TD in elderly
- Saltz 1991, Pospective study td incidence-elderly
- Woerner 1998, Prospective study of TD in elderly
- Yassa 1988, TD biological mechanisms and clinical aspects
- Yassa 1992, TD in elderly a 5 yr 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. Estimated TD prevalence rates in children vary widely but are generally very high at “8%-51% of antipsychotic-treated children and adolescents” (Cozza et al., 2003). p. 1422).
- APA 1992, Task Force guidline
- Connor 2001, TD Atypicals Children
- Cozza 2003, APA Textbook, childhood TD
- Gualtieri 1988, Tardive Dyskinesia
(4) 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 (10) below with more than two dozen reports of tardive dyskinesia caused by Risperdal published prior to 2005.
- Abilify 2011, Full prescribing informaiton
- Abilify 2014, Full prescribing info
- Chouinard 2008, Atypicals CATIE
- Kapur 1999, Clinical implications of dopamine blockade
- Lieberman & Stroup 2011, Emperor’s new clothes, CATIE study results
- Lieberman CATIE 2005, effectiveness & adverse effects
- Miller 2008, TD & EPS from 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
- Stroup & Lieberman 2010, CATIE TD same
- Woods 2010, TD from atypicals.
(5) 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 2012, 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 akathisia
- Gualtieri 1988, Tardive dyskinesia
- Ho 2011, Antipsychotics and brain atrophy
- Khorram 2006, Antipsychotics and bran atrophy
- 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.
(6) 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
- Liddle 2000, Effects of risperdal basal ganglia
- Robinson 2008, Basal ganglia learning memory.
(7) Tardive Dystonia is a variant of tardive dyskinesia (TD) that has been recognized for decades in the scientific literature. It shares many basic characteristics with TD in general, except it is characterized by tension and spasms in the muscles, and can be very painful. Some of the articles in this section will make comparisons to “classic TD” and some will discuss the rates.
- Breggin note on dystonia rates
- Burke 1982, Tardive dystonia late onset
- Defazio 2013, Cervical dystonia
- Dew 2004, Ziprasidone dystonia EPS
- Duggal 2007, Ziprasidone and tardive dystonia
- Gunal 2001, Tardive dystonia from Zyprexa
- Kiriakakis 1998, Dystonia review rates
- Lewitt 1995, Drug-induced dystonia
- Sachdev 1993, Clinical characteristics of tardive dystonia
- Steeves 2012, Dystonia meta-analysis
- Tsai 2008, Ziprasidone and tardive dystonia
- Yassa 1985, Prevalence of tardive dystonia.
(8) Tardive Akathisia is a variant of tardive dyskinesia that has a powerful emotional component. An inner agitation that feels like being tortured from the inside out drives people to keep moving in a vain effort to find relief. Attempts to describe these feelings often impress hasty diagnosticians as evidence for delusions and hallucinations. Many such patients end up getting more of the drug that is driving them over the edge. The movements vary from running and pacing to tapping feet, wringing hands or squirming. I have seen people contain them for a while with great effort. Other people end up with the agitated feeling, even though they have not been or are no longer feelings driven to move about. Although little is written about it, I have found that paresthesias (abnormal feelings in the skin) often go along with akathisia, including crawling and burning sensations that may at times be felt inside the mouth as well. This condition is caused by both SSRI antidepressants and antipsychotic drugs. Among the antidepressants, Paxil may be a special offender. Among the antipsychotic drugs, Abilify is far the clear leader in causing it. The Full Prescribing Information for Abilify, found in this section, even calls it “common.” So does an Abilify advertisement contained here. Akathisia always worsens a person’s condition and can lead to psychosis, violence, and suicide. These dreadful outcomes from both SSRIs and antipsychotic drugs were recognized in the APA’s Diagnostic and Statistical Manual of Mental Disorders found in this section.
- Abilify Label 2014
- Ablify Advertisement 2014
- DSM-IV-TR 2000, Akathisia
- Gualtieri 2002, Tardive dyskinesia & akathisia
- Gualtheri 1993, Tardive dyskinesia & akathisia
- Poyurovsky 2010, Akathisia CATIE editorial
- Poyurovsky 2010, Akathisia including Abilify
- Stroup & Lieberman 2010, CATIE TD same
- VanPutten 1975, The many faces of akathisia
- VanPutten Marder 1987, Behavioral toxicity of antipsychotics
- Miller 2008, TD & EPS from atypicals
- VanPutten 1974, Phenothiazine-induced decompensation
- VanPutten 1974, Why people refuse antipsychotics
- VanPutten 1975, Prolixin decompensation
- VanPutten1980, Subjective responses to thiothixene.
(9) Neuroleptic Malignant Syndrome (NMS). Although neuroleptic malignant syndrome (NMS) is not a form of TD, if the individuals survive, NMS can leave them with a wide variety of symptoms associated with TD, including abnormal movements and cognitive changes. The classic symptoms of neuroleptic malignant syndrome are (1) fever; (2) abnormal movements, such as rigidity, Parkinsonism, and TD-like reactions; (3) worsening mental status, and (4) autonomic nervous system dysfunction, such as rapid respirations, elevated pulse, unstable blood pressure, chills, sweating, and incontinence. However, in my clinical experience and confirmed in the literature (Levinson and Simpson, 1986, see below), NMS or NMS-like disorders caused by antipsychotic drugs can have many variable forms, intensities and durations. These drug-induced disorders, with or without a fever, must be recognized and the medications removed in order to prevent serious and potentially lasting harm.
I was probably the first scientist to observe that an acute case of NMS is indistinguishable from an acute episode of an epidemic called lethargic encephalitis that was recognized during the First World War and spread during the following decade (see my 1993 article in this section).
- Aripiprazole and NMS child Palakurthi 2007
- Aripiprazole and NMS Hammerman 2006
- Aripiprazole and NMS Spalding 2004
- Aripiprazole and NMS Strawn 2006
- Aripiprazole NMS Brunelle 2007
- Aripiprazole NMS Evcimen 2007
- Aripiprazole NMS Strephichit 2006
- Ariprazole and NMS Chakraborty 2004
- Berman 2011 NMS
- Breggin 1993 NMS compared to lethargic encephalitis
- Caroff NMS 3% 1993 neuroleptic malignant syndrome
- FDA 2006 Seroquel warning letter NMS TD
- Levinson 1986, NMS with fever
- Nisimima 2013, Creatine kinase in NMS
- Olanapine NMS Zyprexa memory loss Mendhekar 2006
- Pelonero 1998 Review NMS
- Sachdev 2005 NMS rating scale
- Strawn 2007 Scope and nature of NMS
- Symptoms of NMS, Addonizio 1986
- UpToDate 2014, Be on alert for NMS
- Wojcieszek 1998 NMS TD.
(10) 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 have known early on that so-called atypicals would cause TD. This section contains nearly two dozen clinical reports of Risperdal-induced TD published before 2005, including several cases involving children.
- 1995 Risperdal TD, Addington
- 1996 Risperdal TD, Anand
- 1996 Risperdal TD, Buzan
- 1996 Risperdal TD in 18 children, Daniel
- 1996 Risperdal TD in child, Feeney
- 1996 Risperdal TD cases 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 4 cases, Campbell
- 1999 Risperdal TD, Vercueil
- 2000 Risperdal TD in child, Kumar
- 2001 Risperdal TD, Ipekci
- 2001 Risperdal TD, Morgensternre
- 2002 Risperdal TD, Vasudevan
- 2004 Risperdal TD, Adamou
- 2004 Risperdal TD in child, Kwon.
(11) 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).
(12) Criminal and civil fines imposed on Johnson and Johnson, or 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 secretly and illegally paid Harvard psychiatrists Joseph Biederman, Thomas Spencer, and Timothy Wilens to promote Risperdal to children for the invented diagnosis of childhood bipolar disorder (Sarchet, 2011; Yu, 2011). This caused a forty times increase in children diagnosed with bipolar disorder between 1994 and 2003 (Moreno et al., 2007).
- J&J, Has a new image campaign, but some things don’t change
- Moreno 2007, 40x increase in bipolar diagnoses
- NYT describes $2.2 billion settlement
- Risperdal, Texas v Janssen complaint T-map algorithm
- Rothman 2010, expert report Texas v J&J, risperdal
- Sarchet 2011, Psychiatrists hid drug-company links
- United States’ Civil Complaint
- U.S. Dept of Justice, Johnson & Johnson case documents
- Yu 2011, Psychiatrists hid drug-company ties.
(13) 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
- AGS 2012, Scientific paper on medications for elderly
- AGS 2015, Beers criteria elderly and medication
- AGS 2015, Beers criteria for medicating elderly
- APA 1985, Letter warning about TD to association membership
- APA 1992, Task force guidelines
- APA 1999, Textbook of Psychiatry (TD) and later editions
- Cozza 2003, APA Textbook, childhood TD
- Haag 1992, WHO recommended documentation.
(14) 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.
(15) 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
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.