Psichiatria

Adan Lanza ha agito sotto gli effetti di psicofarmaci

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DECEMBER 21, 2012

Adam Lanza Taking Antipsychotics

Via Business Insider, hat tip  SBY News:

The Antipsychotic Prescribed To Adam Lanza Has A Troubled History All Its Own:

By now the whole country is fully embroiled in the Gun Control debate, spurred by the grisly murder of 27 people, mostly kids, at the Sandy Hook Elementary school last Friday.Fanapt

Guns might not be the only problem though.

New York Magazine wrote a pieceabout shooter Adam Lanza’s supposed “aspergers” syndrome as a “red herring” meant to distract from the real problem (guns, of course, the subject goes without mentioning).

Inside the piece though they report the boy was prescribed Fanapt, a controversial anti-psychotic medicine.

The article uses the term “controversial” to describe Fanapt, one generic name used for the drug Iloperidone which is an atypical antipsychotic  medication that works by changing the effects of chemicals in the brain.  Fanapt is used to treat schizophrenia andmay also be used for purposes not listed in the medication guide.

From Wikipedia:

Iloperidone, also known as FanaptFanapta, and previously known as Zomaril, … It was approved by the U.S. Food and Drug Administration (FDA) for use in the United States on May 6, 2009.
As most people know, the medication guides are written by lawyers and included with all medications these days.  They list every possible side affect that could ever happen even to a tiny percent of those taking the medication. The medication guide is more of a ‘cover your butt’ for the drug companies than it is a caution for the consumer.  It does say that thoughts about suicide or hurting yourself can be a side affect of Iloperidone.

Drugs.com also reports:

 Psychiatric side effects including restlessness, aggression, and delusion have been reported frequently. Hostility, decreased libido, paranoia, anorgasmia, confusional state, mania, catatonia, mood swings, panic attack, obsessive-compulsive disorder, bulimia nervosa, delirium, polydipsia psychogenic, impulse-control disorder, and major depression have been reported infrequently. (hat tip Economic Policy Journal)

InfoWars writes:
As the except from CCHR below demonstrates, anti-psychotic drugs are a hallmark of mass shooters, but you won’t see any call in the mainstream media to see them banned, …

What caused Adam Lanza to shoot his mother in the face, to shoot 20 innocent young children and 6 innocent adults and then shoot himself?  We may never know.  To blame it on a prescription alone that was supposed to help him is wrong; or to blame it on video games alone is wrong;  to blame it on his mental condition alone is wrong.  To blame the 27 deaths on a a gun that on it’s own can do nothing, is certainly wrong.

Lanza had problems, his mother was apparently trying to get him into a facility that could help him, and he did not want to go, according to some reports.  Other reports have the mother trying to push him out of the house to get a job or attend college.

We may never really know the truth.

Back to the drug from Business Insider:

Fanapt was the subject of a Bloomberg report when it passed regulators, after previously getting the “nonapproval” stamp. Why wasn’t it approved, you might ask?

There are many reasons, some of which have to do with competing entities in a competitive market.

The main cited reason for the rejection was that it caused severe heart problems in enough patients to cause a stir.

Maybe more importantly, though, Fanapt is one of a many drugs the FDA pumped out with an ability to exact the opposite desired effect on people: that is, you know, inducing rather than inhibiting psychosis and aggressive behavior.

[snip]

In fact, Fanapt was dropped by its first producer, picked up by another, initially rejected by the FDA, then later picked up and mass produced. The adverse side-effect is said to be “infrequent,” but still it exists, and can’t be ignored.

The reaction invoked by the drug in some people is reminiscent of the Jeffrey R. MacDonald case, where a Green Beret slaughtered his entire family and then fabricated a story about a marauding troop of “hopped up hippies”.

MacDonald though, had Eskatrol in his system, a weight-loss amphetamine that’s since been banned in part for its side effects of psychotic behavior and aggression.

These drugs are not the only ones that can cause the opposite of their desired effect. Several anti-depressant medications are also restricted to adults, for the depression they inspire in kids rather than eliminate.

Fanapt (iloperidone)

Side Effect Search
Underlined words or phrases provide helpful links to information in wikipedia.org and when moused over often give helpful definitions of the medical terms. Keywords
Fanapt may cause aggressive/violent behavior (frequent).This drug may also cause the following symptoms that are related to aggressive/violent behavior:

Medical Source Information
Yellow highlights indicate symptoms related to aggressive/violent behavior.Psychiatric side effects including restlessnessaggression, and delusion have been reported frequently. Hostilitydecreased libidoparanoiaanorgasmiaconfusional statemania,catatoniamood swingspanic attackobsessive-compulsive disorderbulimia nervosa,deliriumpolydipsia psychogenic, impulse-control disorder, and major depression have been reported infrequently.Nervous system side effects including dizziness (up to 20%), somnolence (up to 15%),extrapyramidal disorder (up to 5%), tremor (3%), and lethargy (up to 3%) have been reported.Paraesthesia, psychomotor hyperactivity, restlessnessamnesia, and nystagmus have been reported infrequently. Restless legs syndrome has been reported rarely.

Side Effects to Watch
Watch closely for the following side effects and notify your physician immediately should any of these develop:
  • Abnormal heart rate, fluttering in the chest, weakness, faintness, dizziness or loss of consciousness (signs of a serious condition called “torsade de pointe or QT prolongation” in which irregular heartbeats occur)
Lab and Diagnostic Tests
If certain symptoms develop, ask your physician whether you need the following lab tests or other diagnostic tests (if you’ve not already had them):
  • Monitor white blood cell count, complete blood count and complete blood count
  • Blood tests to assess normal clotting – in people who develop signs of bleeding such as abnormal bruising or signs of bleeding including bleeding from the gums, nose, digestive tract, vagina (females), faintness, dizziness, loss of consciousness, or rash
  • EKG – if abnormal heartbeats (rapid slow or irregular) develop
  • electrolytes, magnesium, potassium and glucose – check before starting treatment and then periodically
References
  1. Product Information. Fanapt (iloperidone). Anonymous Vanda Pharmaceuticals Inc, Rockville, MD.


Standard
Psichiatria

Psicofarmaci e violenza

violenzaNeuroleptic Drugs and Violence

 

Catherine Clarke SRN, SCM, MSSCH, MBChA.

and Jan Evans MCSP. Grad Dip Phys.

August 19th, 2012

Introduction

 

We address the fact that the treatment for Severe Mental Illness (SMI) is neuroleptic medication. One has to give significant thought about the involvement of neuroleptic medications with the tragic circumstances of individuals who have perpetuated a progressive catalogue of catastrophic actions, and the many victims and their families who so sadly are caught up in such tragedies.

 

It is established that there is an increased risk of violence by people with a mental health diagnosis. A greater risk of violent behaviour (27.6%) has been found for patients who commit substance abuse, compared to non-abusers (8.5%). For patients with schizophrenia, 13.2 % committed at least one violent offence, compared with 5.3% of the general population.1

 

Violence is reported with command hallucinations: 48% experienced harmful or dangerous actions and this increased to 63% in medium secure units and was significantly higher, 83%, in the forensic population.2

 

People who are classified as SMI i.e. with schizophrenia or bipolar often experience violent incidents following a diagnosis of SMI, even though they don’t consume alcohol or use street drugs, nor having a past history of violence or command hallucinations to harm others.

Our purpose of this document is to provide a referenced explanation of how neuroleptic medications are a potential cause of violence. We take a physiological perspective concerning pharmacogenetic variants and the disruption of neurotransmitters. In Part 1 we discuss what is known about Neuroleptics and Neurotransmitters; in Part 2, the Neuroleptic Disruption of Neurotransmitters

 

Part 1

 

The first part of this document has the following structure:            

·       Violence

  • Neuroleptic Adverse Effects on Behaviour
  • Serotonin Disruption
  • Noradrenaline/Norepinephrine Disruption
  • Acetylcholine Disruption including Neuroleptic Malignant Syndrome and Organophosphate Poisoning

·       Neuroleptic Withdrawal Adverse Effects on Behaviour

·       Neurotransmitter Functioning and Behaviour

·       Increased Prescribing of Neuroleptics as a Risk for Increased Violence

 

Violence

This is an important issue. In three acute psychiatric units in Australia it was reported: “58 % of the incidents were serious violent incidents.”3 In an attempt to address psychiatric violence in the UK, the National Institute for Health and Clinical Excellence (NICE) has a full clinical guideline: Violence. The short-term management of disturbed/violent behaviour in in-patient psychiatric settings and emergency departments.4 Although this addresses many issues, it omits the following potential causes of violence:

  • Neuroleptic medications – due to neuroleptic disruption of neurotransmitter circuits such as dopamine, serotonin, norepinephrine/noradrenaline and acetylcholine.
  • Pharmacogenetics – the issue of inefficient neuroleptic metabolising.

 

Adverse Effects on Behaviour of Neuroleptics

 

Neuroleptic toxic adverse reactions are related to behavioural changes such as akathesia, which is known to be a predisposing factor to violence5 and was formally recognised in the late 1970s.6

 

The symptoms of akathisia, an extreme, involuntary internal physical and emotional restlessness, includes restlessness, agitation and irritability.

 

When there is an existing precondition of akathisia, any perceived untoward disrespectful attitudes or verbal communications can trigger violence. When patients are agitated or irritable, they are less able to cope with perceived disrespect and are more prone to respond violently.

 

A marked increase of violence has occurred with patients prescribed moderately high-doses of haloperidol,7 and with Asian patients clozapine played a role in causing aggression and disruptive behaviour.8 Both the older ‘typical’ and the newer ‘atypical’ neuroleptics are associated with adverse behavioural reactions in a study reporting that “the newer antipsychotics did not reduce violence more than perphenazine.”9

 

Chart Depicting Toxic Behavioural Effects for Typical Neuroleptics:

 

 

Typical Neuroleptics

 

 

Adverse Reactions Related to Violence

Clopixol Agitation & akathisia
Haloperidol Restlessness, agitation and violence
Stelazine Restlessness
Sulpiride Restlessness & akathisia

 

 Refs 7, 10 &11

 

Chart Depicting the Toxic Behavioural Effects for Atypical Neuroleptics:

 

           

Atypical Neuroleptics

 

Adverse Reactions Related to Violence

Abilify Restlessness, agitation and akathisia
Amisulpride Agitation

Clozaril

Akathisia and agitation
Olanzapine Restlessness and agitation
Palperidone/Invega Akathisia and aggression
Quetiapine Akathisia and irritability
Risperidone Agitation
Sertindole Akathisia
Zotepine Akathisia

 

Ref 10

                       

Observations in prison have also associated neuroleptic treatment with increased aggressive behaviour. Inmates were better able to control their aggression until they were prescribed neuroleptics and then the aggression rate almost tripled.12

 

Neuroleptic Withdrawal Adverse Effects on Behaviour

 

There is also the issue of violence experienced during withdrawal. Irritability and agitation is reported in association with neuroleptic withdrawal,13 and a direct reference links akathisia following the withdrawal of a depot in an inpatient setting.14 Irritability, agitation and akathisia need to be recognised as reactions to neuroleptic withdrawal. 

In order to prevent violence in association with akathisia and withdrawal, this process needs to be undertaken by a professional or lay-person who understands the potential problems and can therefore guard against unwittingly appearing at all antagonistic to the patient.

Neurotransmitter Functioning and Behaviour

 

Fundamentally, human behaviour is determined by neurotransmitter functioning and “A rich literature exists to support the notion that monoamine (i.e. serotonin, dopamine, and norepinephrine) neurotransmitter functioning is related to human aggressive behaviour.”15

 

Dopamine, serotonin and all other neurotransmitter circuits are interdependent and any disturbance in one will result in an imbalance in them all, disrupting normal functioning. Jackson’s First Law of Biopsychiatry states:  “For every action, there is an unequal and frequently unpredictable reaction.”16

 

Chronic neuroleptic treatment causes unpredictable behavioural reactions due to dysregulation and disruptions between dopamine, serotonin and acetylcholine neurotransmitters.

 

Neuroleptics and Serotonin Disruption

 

Some neuroleptics are known as serotomimetic drugs, affecting serotonin receptors – some block the receptors and some make them more active. “There are 14 different types of serotonin receptors that may be targeted by neuroleptics, with risperidone, clozapine, olanzapine, quetiapine and clopixol especially affecting the serotonin 5-HT2 receptor.”17 

           

Mental status changes occur in Serotonin Syndrome. This is caused by neuroleptic drugs due to serotonin toxicity.

Animal research indicates that serotonin disruption is associated with increased violence. Reduced levels of a specific serotonin metabolite (5-HIAA) in cerebrospinal fluid has been linked with increased aggression in both dogs and male rhesus macaques18-19 and low concentrations of 5-HIAA in different cultures have been consistently reported to be associated with impulsive destructive behaviours, aggression and violence.20

 

Since “Impulsive violence is closely linked to serotonergic function and to several brain regions”21 and since impulsivity is also linked with both low and high serotonin levels it is difficult to know which of these changes play the most important role in treatment emergent violence.”17 

 

The reciprocal interaction between the dopaminergic and serotonergic systems disturbed by either dopaminergic blockers or serotonergic enhancers leads to the disruption of homeostasis.22 Although the serotonin system and its interactions with other neurotransmitters are complex and full information is difficult to find, there are clear research papers, which show that serotonin and aggression are related.

 

Chart depicting Neuroleptic Serotonin Disruption associated Adverse Toxic Behavioural Effects:

Akathisia Irritability
Suicidality

Violence

Arson Aggression
Violent Crime Self Destructiveness
Impulsive Acts Agitation
Hostility Violent Suicide
Argumentativeness

 

Ref 23 & 24

 

Neuroleptics and Noradrenaline/Norepinephrine Disruption

 

Neuroleptics affect the norepinephrine neurotransmitter and akathisia induction with haloperidol is known to be associated with increased noradrenaline turnover.25- 26

 

Neuroleptics and Acetylcholine Disruption

 

An important function of the acetylcholine neurotransmitter is the control of psychological defence mechanisms including fight or flight responses.  Such responses are impulsive and naturally include aggression and violence.

 

In varying degrees, all neuroleptic drugs have anticholinergic properties. This means that they block and cause disruption to the acetylcholine neurotransmitters. The body compensates and responds by making and releasing more acetylcholine.27

 

Acetylcholine Disruption and Increased Violence

 

Aggressive responses such as defensive rage and violence have been linked with excessive acetylcholine in animals28 –30 and a relative acetylcholine increase is associated with neuroleptic drugs due to the disruption of the dopamine-acetylcholine equilibrium.31-32

 

Since excessive acetylcholine is linked with aggression and violence in animals, it is likely that neuroleptic induced acetylcholine abundance triggers aggression and violence in humans.

Neuroleptic → Disrupted dopamine-acetylcholine equilibrium → Relative acetylcholine increase → Aggression/Violence.

 

Neuroleptic Malignant Syndrome and Organophosphate Exposure

 

Neuroleptic Malignant Syndrome (NMS) is an adverse effect of neuroleptics, a potentially fatal condition with up to 76% mortality rate.  Symptoms of NMS include aggression, agitation and violence.27 & 33 New research associates NMS with elevated acetylcholine.34

 

Organophosphate chemicals form the basis of many insecticides, herbicides and nerve gases. They block the action of the body’s acetylcholinesterase enzyme, which breaks down acetylcholine so it may be processed and recycled. Excessive acetylcholine accumulates in the nervous system if the action of this enzyme is blocked.

 

Prolonged and repeated exposure to Organophosphates results in Chronic Organophosphate-Induced Neuropsychiatric Disorder (COPIND) e.g. in farmers who handle pesticides, due to chronic Organophosphate Poisoning (OP). COPIND behavioural symptom changes include: Hostility, Anger, Aggression and Violence.35-36  Since OP results in excessive acetylcholine, which is linked with aggression and violence in animals, the behavioural changes in COPIND are highly likely caused by excessive acetylcholine.

 

The link between Neuroleptic Malignant Syndrome and Organophosphate Poisoning

 

The symptoms of NMS and OP are similar. In both NMS and OP the replication of symptoms is due to autonomic instability and stems from disruption of the acetylcholine circuits and transmitters of the Autonomic Nervous System, involved with vital involuntary functions.

 

Autonomic Instability includes profuse sweating, high blood pressure, low blood pressure, respiratory distress, drooling, urinary or faecal incontinence, increased and

decreased heart rate.27

Chart Depicting the Symptom Similarities of NMS and OP

 

 

Neuroleptic Malignant Syndrome

 

Organophosphate Poisoning

 

Autonomic nervous system disturbance Autonomic Instability

Aggression, agitation and violence

Aggression
Muscle rigidity Paralysis, Dystonia, Cranial nerve palsy and polyneuropathy                                                                                                                                                                   
Muscle breakdown Weak respiratory and limb muscles
Coma, alterations of consciousness Loss of consciousness
Confusion Dementia, psychosis, anxiety, depression
Fever Seizures

 

Refs 27 & 33

Conclusion: Organophosphates, Neuroleptics and Violence

 

Organophosphate Poisoning results in over stimulated acetylcholine neuro-circuits and systems. The action of neuroleptics is similar.  It is generally accepted that Organophosphate Poisoning results in behavioural changes including violence.

 

Despite research to show that neuroleptics are associated with disrupted acetylcholine, it is not yet generally accepted that neuroleptics are a potential cause of violence.

 

Antipsychotic/neuroleptic drugs have strong anti-cholinergic properties and long-term use causes behavioural changes, which replicate the same behavioural changes occurring in chronic Organophosphate Poisoning:  

 

“This adaptation (to psychiatric drugs – author input) replicates the effect of organophosphate poisoning whether by nerve gas, by insecticide, or by anti-Alzheimers pharmaceuticals by over stimulating acetylcholine circuits of the brain.”27  

 

Increased Prescribing of Neuroleptics

 

There has been a distinct increase in neuroleptic medications, prescribed as part of treatment for mental health issues.

 

In the UK between 1998 and 2010, Neuroleptic drug prescriptions increased by an average of 5.1% every year.37 Over twelve years, this is a total increase of 60%.

 

In England, the approximate number of neuroleptic and depot (injection) prescriptions used by outpatients:

2008 – 7.0 million

2009 – 7.3 million

2010 – 7.6 million

2011 – 7.9 million38

 

However, due to confidentiality, the data for the number of neuroleptic prescriptions in inpatient settings is not made available. So the actual total increase of neuroleptic prescriptions in the UK is unknown.

 

Increased Prescribing as a Risk for Increased Violence

 

 

As outlined above, neuroleptics are a possible cause of violence. With ever increased prescribing of neuroleptic medications, it is reasonable to expect an increased amount of violent behaviour amongst those with a severe mental health diagnosis.

 

Since neuroleptic prescriptions are increasing by 300,000 per year in the UK, it is hypothesized that the rise in violence for neuroleptic-treated patients will escalate, whether in the community or in acute wards, secure units, prisons or outpatient units.

 

Part 2. Neuroleptics and Pharmacogenetics

 

The second part of this document has the following structure:

  • Introduction to Pharmacogenetics regarding Neuroleptics
  • Pharmacogenetics and Ethnic Black Populations
  • Black Populations and Psychiatric Intensive Care Units
  • Black Populations, detention under the UK Mental Health Act and UK Community Treatment Orders
  •  Pharmacogenetics as an explanation for Black Over-representation in

Psychiatric Intensive Care Units, detentions within the UK Mental

Health Act and Community Treatment Orders

­­­­­­­­­­­­­­­

Introduction to Pharmacogenetics with regards to Neuroleptics

 

Pharmacogenetics is the science of how drugs are broken down and used – i.e. metabolised in the body, mainly in the liver, by the genetically diverse Cytochrome P450 (CYP450) enzyme system and other drug metabolising systems. There are many CYP450 variants that affect therapeutic efficacy and inefficacy of medications.

 

Extensive Metabolisers are efficient metabolisers, whereby side-effects do not build up. Poor Metabolisers are inefficient metabolisers that have no metabolising activity whatsoever; this means that drug toxicities do build up and cause side effects. Intermediate Metabolisers have approximately 50% drug metabolising capacity and produce lesser side-effects than Poor Metabolisers.39 Ultra Rapid Metabolisers/ Hyperinducers have higher than normal rates of drug metabolism; Those medications which are classified as prodrugs are inactive until metabolised in the body, therefore Ultra Rapid Metabolisers are at increased risk of drug-induced side effects due to increased exposure to prodrug active drug metabolites.40

 

Neuroleptic drugs are metabolised through CYP450 enzymes e.g.CYP450 1A2, 2D6 and 2C19. A single neuroleptic can necessitate a combination of CYP450 enzymes for metabolisation.

All SMI patients who are Poor and/or Intermediate Metabolisers of neuroleptics, and Ultra Metabolisers of neuroleptic prodrugs; e.g. paliperidone, the active metabolite of risperidone; will inevitably suffer neurological and behavioural changes due to toxicities incurred from the inability to metabolise neuroleptics efficiently. Polypharmacy compounds the toxicities.

 

CYP450 1A2 Metabolising Pathway and Neuroleptics

CYP450 1A2 enzyme pathway has many variants and metabolises olanzapine and haloperidol and is the major metabolising enzyme for clozapine.

 

CYP1A2*1C and *1D Poor Metabolisers have been associated with increased clozapine exposure and adverse reactions.41 CYP1A2*1K is also Poor Metaboliser genotype.42

 

In one study, Asian patients who were prescribed clozapine, experienced aggression and disruptive behaviour who, following clozapine discontinuation, had marked improvement.8 The genotype of the Asian patients in the study is unknown, however since 25% of Asians have CYP1A2*1C Poor Metaboliser genotype,43  it is possible these patients were either CYP1A2*1C, *1D or *1K or a combination of these Poor Metaboliser genotypes.

 

Additionally15-20% of Asians are Poor Metabolisers for CYP2C19 and 2% are Poor Metabolisers for CYP2D6.44CYP2C19 and CYP2D6 metabolise clozapine as well as CYP1A2; any of these combinations are possible and could have predisposed to disruptive behaviour.

CYP450 2D6 Metabolising Pathway and Neuroleptics

 

75% of all psychotropic drugs, including neuroleptics, are metabolised via CYP450 2D6.45 CYP450 2D6 is a highly variable enzyme with a significant percentage of the population being Poor, Intermediate or Ultra Metabolisers and is linked with a poor therapeutic response and adverse reactions.

 

Violence in relation with serotonin toxicity/akathisia has been linked with pharmacogenetic CYP450 2D6 drug metabolising variants.46

 

Pharmacogenetics and Ethnic Black Populations

 

Due to genetic variations there is higher incidence of Poor Metaboliser and Ultra Metaboliser status in Black populations, compared with White and Asian populations for the CYP 450 2D6 pathway. “The prevalence of poor metabolizers in Black populations has been estimated from 0 to 19%, compared with consistent reports of   poor metabolizer status in Caucasians (5–10%) and Asians (0–2%).”47

 

Recalling that 75% of neuroleptic medications are metabolised via CYP450 2D6, the following table shows the variation of metabolising ability in black ethnic populations for CYP450 2D6.

 

 

Poor Metabolisers

Ultra Metabolisers

South Africans

18.8%

Nigerians

8.6-8.3%

Ghanaians

6%

African – American

3.9%

2.4%

Zimbabwean

2%

Tanzanian

2%

American Black

1.9%

Ethiopians

1.8%

29%

 

Ref 48

 

29% of Ethiopians and 2.4% of North African Americans are Ultra Metabolisers via CYP450 2D6 pathway.48 Furthermore, 10-20% of Africans are Poor Metabolisers and 5% are Ultra Metabolisers via CYP450 2C19.49

 

Many prescription medications can lead to “serious mental change.”50 Since black populations statistically have difficulty in metabolising general and psychotropic medications and cannabis via the CYP450 pathways, this factor could contribute to  BME groups living in the UK who are more likely to be diagnosed with a Mental Health problem and admitted to hospital.51

 

 

Psychiatric Intensive Care Units and Over-representation of Black Populations

In UK Psychiatric Intensive Care Units (PICU), there is clear over-representation of black ethnic patients.52 Another study showed fifty-five percent of PICU admissions came from ethnic minorities(compared with 25.6% of total hospital admissions and 20.9%of the local catchment area population aged between 16 and 65years).53

“TypicalPICU patients are male, younger, single, unemployed, sufferingfrom schizophrenia or mania, from a Black Caribbean or Africanbackground, legally detained, with a forensic history. The mostcommon reason for admission is for aggression management.”54

 

UK Mental Health Act Detentions and Over-representation of Black Populations

There is also a disproportionately large representation of Black Minority and Ethnic (BME) origin when considering those who are legally detained under the UK Mental Health Act.

The proportion of black and black British people legally detained rose by 9.7%, with a 9% rise in the number of Asian or Asian British and mixed-race people detained for treatment, compared to a 0.3% rise for the overall number of people detained from 2007/8 to 2008/9. This disparity grew and 53.9% of black/black British inpatients spent time compulsorily detained, as did almost half of mixed-race inpatients and over 40% of Asian/Asian British inpatients, compared with 31.8% of all psychiatric inpatients who spent some time detained during the year.55

 

UK Community Treatment Orders and Black Populations

Legal UK Community Treatment Orders are enforced when patients have received mental health ‘treatment’ i.e. neuroleptics and history of violence; BME Groups have more Community Treatment Orders than white populations.56

“There is a possible relationship for psychiatric in-patients between compulsory detention, disturbed behaviour, depot medication and being black, which is not satisfactorily explained by diagnosis alone.”57

 

The higher incidence of mental health problems in black populations is most likely due to the higher incidence of Poor, Intermediate and Ultra Metabolisers and the associated problems with metabolising medications.

 

Synopsis

Neuroleptics can be a cause of violence due to neurotransmitter disruption.

 

Violence must be considered not simply as an indication of how deeply schizophrenia /bipolar illness can worsen, but as an adverse effect of neuroleptic treatment.

 

People who are inefficient metabolisers are likely to suffer more severe adverse effects and become violent or aggressive.

 

BME populations have a higher incidence of inefficient metabolisers and as such a higher incidence of violence leading to PICU admissions and Mental Health Act detentions.

 

However whatever the nationality, when individuals are Poor and Intermediate Metabolisers and Ultra Rapid Metabolisers for prodrugs, the impact of neuroleptics in triggering akathisia, aggression or irritability can trigger violence indiscriminately.

 

Conclusion

There is a larger incidence of violence in people with a severe mental health diagnosis than in the general population. The severely mentally ill are invariably treated with neuroleptic medication which itself can be the cause of violence since neuroleptic medications disrupt neurotransmitter functions. This disruption of neurotransmitter functioning can precipitate violent behaviour. Withdrawal of neuroleptic medication – due again to the disruption of neurotransmitters – is also associated with violence.

 

Pharmacogenetics show that the some people are unable to metabolise neuroleptic medication and this inability can result in further disruption of neurotransmitter functioning with a likelihood of increased violence.

The inability to metabolise neuroleptic medication is particularly prevalent in BME populations. As a consequence this population experience more violence which is confirmed in practice by an over representation of BME individuals, both on Psychiatric Intensive Care Units (PICUs) where a common reason for admission is aggression, and the use of Mental Health Act detentions and Community Treatment Orders.

 

With the trend towards increased prescribing of neuroleptic medications, a level of increased violence can be anticipated for the future.

 

There is the possibility of ameliorating the presence of violence in the severely mentally ill by ensuring pharmacogenetics is more fully recognised as a significant factor, and that genotype testing is adopted in order to assess the ability of the individual to metabolise neuroleptic medication. Without this testing,

much of the violence in psychiatry can be laid at the door of  psychiatrists and the  pharmaceutical companies.

References:

 

Ref 1 Fazel S, et al, (2009) http://www.ncbi.nlm.nih.gov/pubmed/19454640

 

Ref 2 Birchwood et al. (2011)

http://www.biomedcentral.com/1471-244X/11/155/

 

Ref 3 Owen C. et al, (1998) http://ps.psychiatryonline.org/article.aspx?Volume=49&page=1452&journalID=18

 

Ref 4 http://www.nice.org.uk/nicemedia/live/10964/29715/29715.pdf

 

Ref 5 Crowner ML, et al (1990) http://www.ncbi.nlm.nih.gov/pubmed/1973544

 

Ref 6  GB. Leong, M.D. and JA Silva, M.D. (2003)

http://library-resources.cqu.edu.au/JFS/PDF/vol_48/iss_1/JFS2002173_481.pdf

 

 

Ref 7 John N. Herrera et al (1998)

http://psychrights.org/research/Digest/NLPs/RWhitakerAffidavit/HerreraNeurolepticsandViolence.PDF

 

Ref 8 KA.Mansour, C.Willan and J.Follansbee (2003)  http://bapauk.com/doc/Deteriorationofpsychosisinducedbyclozapine_41.doc

 

Ref 9 Jeffrey W. Swanson et al, (2008) http://bjp.rcpsych.org/content/193/1/37.full

 

Ref 10  Drug Monographs, Prescribing information and UK NICE Guidelines 2007 – 2012. 

 

Ref 11  Jerome L. Schulte, (1985) http://psychrights.org/research/Digest/NLPs/RWhitakerAffidavit/Schulte.PDF

 

Ref 12 D.G. Workman and D.G. Cunningham (1975) page 65

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2274756/pdf/canfamphys00332-0065.pdf

 

Ref 13 MIND  http://www.mind.org.uk/help/medical_and_alternative_care/making_sense_of_coming_off_psychiatric_drugs

 

Ref 14 Theodore Van Putten, (1975)

http://psychrights.org/research/Digest/NLPs/RWhitakerAffidavit/VanPuttenManyFacesofAkathisia.PDF

 

Ref 15 Berman ME, Coccaro EF. Neurobiologic correlates of violence: relevance to

criminal responsibility.” Behav Sci Law. 1998 Summer;16(3):303-18. Review.

http://www.ncbi.nlm.nih.gov/pubmed/9768463  

Ref16 Jackson, Grace E. MD, Appendix D, Transcript of

            “What Doctors May Not Tell You About Psychiatric Drugs”           

Public Lecture, Centre for Community Mental Health UCE Birmingham June 2004

 

Ref 17 Jackson Grace E. (2005)  Rethinking Psychiatric Drugs: A Guide for Informed Consent.  Bloomington, IN: Author House.

 

Ref18 Reisner I, et al, (1996) http://www.ncbi.nlm.nih.gov/pubmed/8861609

 

Ref 19 Mehlman P, et al (1990) http://www.ncbi.nlm.nih.gov/pubmed/7522411

 

Ref 20 Brown GL & Linnoila MI (1990) http://www.ncbi.nlm.nih.gov/pubmed/1691169

 

Ref 21 Muller JL et al (2004) http://www.ncbi.nlm.nih.gov/pubmed/15570500

 

Ref 22 Odagaki (2009) http://www.benthamscience.com/cds/samples/cds4-1/0013CDS.pdf

 

Ref 23 Breggin (2003/4) http://www.breggin.com/31-49.pdf

 

Ref 24 Pert CB. Ph.D., (2001) http://ecommerce.drugawareness.org/Ribbon/SSRIMeds.html

 

Ref 25 Naveed Iqbal, MD, et al, (2007) http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1262

 

Ref 26 Hall LM et al (1995) http://www.ncbi.nlm.nih.gov/pubmed/7543647

 

Ref 27 Grace Jackson MD (2009) Drug Induced Dementia. A Perfect Crime Bloomington, IN: Author House.

 

Ref 28 Siegel A, Bhatt S. (2007) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435345/

 

Ref 29 Stefan M. Brudzynski, et al (1990) http://www.ncbi.nlm.nih.gov/pubmed/2293258

 

Ref 30 Graeff FG. (1994) http://www.ncbi.nlm.nih.gov/pubmed/7916235

 

Ref 31 Imperato A. et al, (1993) “Evidence that neuroleptics increase striatal acetylcholine release through stimulation of dopamine D1 receptors” http://jpet.aspetjournals.org/content/266/2/557.abstract 

 

Ref 32 Donald W. Black, Nancy C. Andreasen – Introductory Textbook of Psychiatry – (2011) 5th Edition p.544 American Psychiatric Publishing Inc.

 

Ref 33 Kasantikul D, Kanchanatawan B, (2006)  http://www.ncbi.nlm.nih.gov/pubmed/17214072

 

 Ref 34 Tanya C. Warwick, et al, (2008)

http://www.nature.com/nrneurol/journal/v4/n3/full/ncpneuro0728.html

 

Ref 35 Davies et al, (2000) http://www.national-toxic-encephalopathy-foundation.org/oppest.pdf

 

Ref 36 Singh S, Sharma N. Neurological syndromes following organophosphate poisoning. Neurol India 2000;48:308. http://www.neurologyindia.com/text.asp?2000/48/4/308/1510

 

Ref 37 Trends in prescriptions and costs of drugs for mental disorders in England, 1998–2010 Stephen Ilyas and Joanna Moncrieff (2012)

http://bjp.rcpsych.org/content/early/2012/03/10/bjp.bp.111.104257.abstract

 

Ref 38 NHS The Information Centre for Health and Social Care  “Copyright © 2012, Re-used with the permission of the Health and Social Care Information Centre.     www.ic.nhs.uk

 

Ref 39 Genelex http://www.healthanddna.com/healthcare-professional/dosing-recommendations.html

 

Ref 40 Genelex http://www.healthanddna.com/healthcare-professional/p450-2d6-genotyping.html

 

Ref 41 Clinical and Translational Science: Principles of Human Research by David Robertson and Gordon H. Williams Academic Press Inc; 1 edition (16 Jan 2009) Chapter 21 page 303

 

Ref 42 Aklillu et al, 2003 CYP1A2 allele nomenclature http://www.imm.ki.se/CYPalleles/cyp1a2.htm

 

Ref 43 Todesco et al (2003) http://www.ncbi.nlm.nih.gov/pubmed/12851801 

 

Ref 44 Asian PM for 2D6 Cozza et al 2003 and Richelson 1997 in Clinical Manual of Geriatric Psychopharmacology  By Sandra A. Jacobson, Ronald W. Pies, Ira R. Katz  Publisher: American Psychiatric Press Inc.; 1 edition (30 Jan 2007) Page 44 & 45

 

Ref 45 Joan Arehart-Treichel (2005)

http://pnhw.psychiatryonline.org/content/40/10/33.1.full

 

Ref 46 Lucire Y, Crotty C, (2011)

http://www.dovepress.com/articles.php?article_id=7993

 

Ref 47 Bradford LD, Kirlin WG. (1998).  http://www.ncbi.nlm.nih.gov/pubmed/11281961

Ref 48 Benny K. Abraham, C. Adithan  (2001)  http://medind.nic.in/ibi/t01/i3/ibit01i3p147.pdf

 

Ref 49 Genelex http://www.healthanddna.com/healthcare-professional/p450-2c19-genotyping.html

Ref 50 APRIL, Adverse Psychiatric Reactions Information Link http://www.april.org.uk/main/index.php?uid=269

Ref 51 Mental Health Foundation – Black and Minority Ethnic Communities 

http://www.mentalhealth.org.uk/help-information/mental-health-a-z/B/BME-communities/

 

Ref 52 Stephen Pereira et al, (2006) 

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=651260

 

Ref 53 Anthony Feinstein  and Frank Holloway(2002)

http://isp.sagepub.com/content/48/1/38.short

 

 

 

Ref 54 Len Bower (2008)

http://www.kcl.ac.uk/iop/depts/hspr/research/ciemh/mhn/projects/litreview/LitRevPICU.pdf

 

Ref 55 Community Care For everyone in social care “Mental Health Act detentions rise sharply for BME groups”  

http://www.communitycare.co.uk/Articles/25/11/2009/113253/mental-health-act-detentions-rise-sharply-for-bme-groups.htm

 

Ref 56 National Mental Health Development Unit. BME Groups and Mental Health – Presentation and Evidence to the Centre for Social Justice Mental Health Review 18 October 2010. www.nmhdu.org.uk/silo/files/bme-groups-and-mental-health-.doc

 

Ref 57 Violence: The Short-Term Management of Disturbed/Violent Behaviour in Psychiatric In-patients and Emergency Departments Guideline, Appendix 1: Ethnicity review evidence tables. p.447 http://www.rcn.org.uk/__data/assets/pdf_file/0003/109812/003017_appendices.pdf

 

 

 

 

 

 

 

 

 

 

Standard
Psichiatria

Brain-DisablingTreatments in Psychiatry by Peter Breggin

694940094001_1409784734001_640-brain

Peter Breggin indubbiamente rivela alcuni aspetti negativi del trattamenti farmacologici che non sempre vengono propagandati con la stessa enfasi di quelli positivi, ammesso e non concesso che questi ultimi esistano in un trattamento a lungo termine: in questo senso ciò che dice è degno di essere preso in considerazione ed attentamente valutato. Dove personalmente non seguo Breggin è nel trasformare la sua battaglia contro gli psicofarmaci in uno scontro ideologico che si avvicina molto alle posizioni di Scientology.  in un suo intervento del 2005 egli ringraziava Tom Cruise  di cui  egli condivideva le opinioni e  difendeva l’appartenenza  alla setta.Lo psichiatra americano assomiglia a Beppe Grillo. Egli  si scaglia a testa bassa contro le case farmaceutiche denunciando  giustamente degli abusi ma non propone niente di seriamente alternativo. Le sue proposte sul piano della psicoterapia ad essere gentili sono inconsistenti dato che  secondo lui le malattie nascono da problemi “spirituali”.  La realtà non materiale umana non è ovviamente “spirito” da contrapporre al corpo, salvo non riproporre, in un modo più o meno larvato, un’impostazione fideistica  che si vorrebbe  superare. Il vero nemico da combattere è l’ideologia religiosa  che impedisce alla psichiatria di sviluppare una capacità ed una mentalità atta ad affrontare sul piano della relazione interumana la malattia mentale. Non si possono demonizzare i farmaci e non combattere con altrettanto vigore tanto per fare un esempio  contro le concezioni freudiane infiltrate nella pratica della psicologia e psicoterapia americana. La polemica, peraltro giusta in molte circostanze, contro il trattamento farmacologico è un terreno facile,aperto al sensazionalismo,  che fa leva su componenti persecutorie , come la paura di essere avvelenati o di subire lesioni da parte di medici incompetenti. Rimane la domanda se sia più dannosa una psicoterapia fatta male od un trattamento a base di benzodiazepine od antidepressivi somministrato da uno psichiatra che crede che quella veramente  sia la cura della malattia mentale.

Brain-DisablingTreatmentsi n Psychiatry

DRUGS, ELECTROSHOCI(, AND THE ROLE OF THE FDA

Peter R. Breggin, MD

/7). /;ltj1 LY~

[~I Springer Publishing Company

Contents

Introduction and Acknowledgments …………………………………………….. xi

  1. 1  The Brain-Disabling Principlesof Psychiatric Treatment ……………………………………………………… 1
  2. 2  Deactivation Syndrome (Chemical Lobotomy)Caused by Neuroleptics ……………………………………………………… 14
  3. 3  Neuroleptic-Induced Anguish, Including Agitation,Despair, and Depression …………………………………………………….. 25
  4. 4  Neuroleptic Malignant Syndrome, Tardive Dyskinesia,Tardive Dystonia, and Tardive Akathisia ………………………….. 35
  5. 5  Neuroleptic-Induced Brain Damage, PersistentCognitive Deficits, Dementia, and Psychosis ………………………. 53
  6. 6  Antidepressants, Including Prozac-Induced Violenceand Suicide ………………………………………………………………………… 77
  7. 7  Lithium and Other Drugs for Bipolar Disorder ……………….. III
  8. 8  Electroshock for Depression …………………………………………….. 129
  9. 9  Stimulants and Other Drugs for Children, Including
    an Analysis of Attention-Deficit Hyperactivity Disorder …… 157
  10. 10  Antianxiety Drugs, Including Behavioral Abnormalities

Caused by Xanax and Halcion ., …… ………………………………….. 184

ix

x Contents
11 Drug Companies and the Food and Drug

Administration: Failed Mandates …………………………………….. 208 Bibliography …………………………………………………………………………… 234 Index ……………………………………………………………………………………… 295

CHAPTER 4

Neuroleptic Malignant Syndrome, Tardive Dyskinesia, Tardive Dystonia, and
Tardive Akathisia

This chapter focuses on two well-known neurological disorders caused by the neuroleptics-tardive dyskinesia (TD) and neuroleptic malignant syndrome (NMS), with emphasis on their frequency and their destructive impact on the physical and emotional life of the individual. It also discusses neuroleptic withdrawal syndrome. The next chapter will explore irrevers- ible damage to the brain that primarily affects mental functioning, includ- ing tardive psychosis and tardive dementia. However, as products of neuroleptic neurotoxicity, all these drug-induced abnormalities are clini- cally and neurologically interrelated.

TARDIVE DYSKINESIA

Within a few years after the development of the first neuroleptic, it became obvious that many patients were not recovering from their drug-induced neurologic disorders even after termination of the therapy. Reports were made in the late 1950s. Delay and Deniker (1968) date their awareness

35

36 Neuroleptic Malignant Syndrome and Relnted Disorders

of irreversible neurological syndromes to 1959. By 1968 they were able to provide a vivid review of several varieties, including buccolingual, tnmcal, and variable choreic movements. In 1964 Faurbye (Faurbye, Rasch, Petersen, & Brandborg, 1964) named the disorder tardive dyski- nesia.

As if governed by one mind, psychiatry as a profession refused to give any official recognition to this potential tragedy. Then Crane made it a personal crusade to gain the profession’s recognition of the problem (1973). The American College of Neuropsychopharmacology/Food and Drug Administration Task Force (1973) described the syndrome in a special report. Following 1973, everyone in the profession should have been alerted to the dangers of TD; but too many psychiatrists have contin- ued to act as if it hardly exists.

In 1980, the American Psychiatric Association (APA) published a task force report on TD. In 1985 the FDA took the unusual step of setting specifically worded requirements for a class warning in association with all neuroleptic labeling and advertising (“Neuroleptics,” 1985). In a wholly unprecedented move, in the same year the APA sent out a warning letter about the dangers of tardive dyskinesia to its entire membership (see chapter 11 for further discussion of the FDA’s role).

TD often begins with uncontrolled movements of the face, including the eyes (blinking), tongue, lips, mouth, and cheeks; but it can start with almost any group of muscles. The most common early sign is a quivering or curling of the tongue. Tongue protrusions and chewing movements are also common, and can become serious enough to harm teeth and impair chewing and swallowing. The hands and feet arms and legs, neck, back, and torso can be involved.

The movements displayed are highly variable, and include writhing contortions, tics, spasms, and tremors. The person’s gait can be badly impaired. More subtle functions can be affected and are easily overlooked: respiration (involving the diaphragm), swallowing (involving the pharyn-

and esophageal musculature), the gag reflex, and speech (Yassa & Jones, 1985).

The movements usually disappear during sleep, although I have seen exceptions. They sometimes can be partially suppressed by willpower; frequently are made worse by anxiety; and can vary from time to time (see below).

Many cases of TD appear to be relatively mild, often limited to move- ments of the tongue, mouth, jaw, face, or eyelids. Nonetheless, they are

frequently disfiguring and often embarrassing. Patients have been known to commit suicide (Yassa & Jones, 1985).

The abnormal movements can sometimes become totally disabling. Turner (1971) describes patients who cannot eat and must have their teeth removed in order to facilitate the entry of food into their mouths. He also describes patients who cannot keep shoes on their feet because they wear them out while sitting with the constant foot-shuft1ing activity. I have evaluated a number of cases in which the tardive dyskinesia was wholly disabling, including massive distortions of the position of the neck or body, rocking and swaying, shoulder shrugging, and rotary or thrnsting movements of the pelvis, as well as disturbances of respiration, such as periodic rapid breathing, irregular breathing, and grunting.

Ironically, the disease makes the patient look “very crazy” because of the seemingly bizarre facial and bodily movements. Tragically, this has often led to patients being treated more vigorously with neuroleptics, ultimately worsening their TD.

As in other neurological disorders, the patient may attempt to hide the disorder by adding voluntary movements to the involuntary ones in order to disguise them. For example, to cover up a tendency to move the arms continually, the patient may make grooming movements around the face and hair. This can make it seem as if the individual suffers from a psychological compulsion instead of a neurological disorder. Or the patient may clasp his arms together in order to control the movements, making it seem as if he is trying to psychologically “hold onto himself.”

All the neuroleptics (see chapter 2 for a list) can cause tardive dyskine- sia, including the atypical neuroleptics clozapine (Weller & Kornhuber, 1993) and risperidone (Addington, Toews, & Addington, 1995). The overall adverse effects of the atypical neuroleptics are summarized in chapter 5.

Masking the Symptoms of TD with Continued Neuroleptic Treatment

The symptoms of tardive dyskinesia are masked or suppressed by these drugs, so that the disease symptoms do not fully appear until the patient has been removed from the treatment. For this reason, in addition to using the smallest possible dose for the shortest possible time, whenever possible patients should periodically be removed from their neuroleptics, if only

38 Neuroleptic Malignant Syndrome and Related Disorders

for a short period, to determine if they are developing tardive dyskinesia. Permanent removal from the neuroleptics is a more difficult matter, often requiring many months of gradual withdrawal for the hrain to adjust to the drug-free environment.

Harold Klawans has discussed the dangerousness of trying to control or treat TD with the causative agent. He asserts (in the discussion following Goetz et al., 1980): “Treatment of tardive dyskinesia with neuroleptics themselves is clearly treatment with the presumed offending agent and should be avoided.” He calls it “short-sighted” to use the neuroleptics in the treatment of tardive dyskinesia, and concludes that the therapy “serves to aggravate its pathogenesis.” Unhappily, Klawans himself in the same article too readily recommends reserpine as a helpful agent in the treatment of TD, when it too can cause the disorder.

Nonetheless, I have seen cases of TD that were so disabling that the only recourse seemed to be treatment with a neuroleptic. But two points must be borne in mind about these cases. First, in each instance, the case became so severe because physicians failed to detect the disorder when it first appeared and continued neuroleptic treatment long after it should have been terminated. This has been true in nearly all the most disabling cases I have examined. Second, the individuals in question were overcome with suffering and rendered wholly unable to function by the TD. They and their families made informed decisions to continue the offending agent because the TD was making life unbearable for the patient.

The anticholinergic drugs typically used to ameliorate the symptoms of drug-induced parkinsonism also may aggravate the symptoms of TD (Yassa et al., 1992). They include benztropine (Cogentin), biperiden (Aki- neton), and trihexyphenidyl (Artane, Tremin). These agents are known to worsen similar symptoms in Huntington’s chorea (Hunter, Blackwood, Smith, & Cumings, 1968; Klawans, 1973). At present the role of these drugs in the development or exacerbation of tardive dyskinesia is contro- versial and undetermined, but caution is required in giving them to patients on neuroleptics. Their adverse effects are discussed in chapter 2. These agents are often used to treat acute extrapyramidal symptoms and may be mistakenly prescribed for TD.

Rates of TD

In 1980 the APA produced a detailed analysis of the disease in its Task Force Report: Tardive Dyskinesia. It made clear that TD is a serious,

Brain-Disabling Treatments in Psychiatry 39

usually irreversible, untreatable, and highly prevalent disease resulting from therapy with the neuroleptics. The task force estimated the prevalence rate for TD in routine treatment (several months to 2 years) as at least 10%-20% for more than minimal disease. For long-term exposure to neuroleptics, the rate was at least 40% for more than minimal disease.

Even after the publication of the 1980 task force report and a mountain of confirmatory evidence, some biologically oriented psychiatrists, such as Nancy Andreasen (1984), in The Broken Brain: The Biological Revolu- tion in Psychiatry, continued to misinform the public that tardive dyskine- sia is “infrequent” (p. 210) and occurs in “a few patients” (p. 211).

The more recent APA task force (1992) report cites a rate of 5% per year, cumulative over the first several years of treatment. Jeste and Caligi- uri (1993) estimate the annual incidence rate among young adults at 4%- 5%.

In a recent prospective project emanating from Yale, Glazer, Morgen- stern, and Doucette (1993) reported a long-term evaluation of 362 outpa- tient psychiatric patients who were free of TD at baseline and who were being maintained on neuroleptics. For patients who are starting neurolep- tics, according to projections from their data, the risk of tardive dyskinesia will be 31.8% after 5 years of exposure-a rate of slightly over 6% per year. The risk is 49.4% after 10 years, 56.7% after 15 years, 64.7% after 20 years, and 68.4% after 25 years.

Chouinard, Annable, Mercier, & Ross-Chouinard (1986) followed a group of 136 persons who had already been receiving neuroleptics but had not manifested TD. Over 5 years, 35%-a rate of 7% per year- developed the disorder.

Overall, in relatively young and healthy patients, the cumulative risk of contracting TD when exposed to neuroleptic~ ranges from 4%-7% per year during the first several years o f treatment. Approximately one-third of the patients will develop this largely irreversible disorder within the

first five years of treatment. This represents an astronomical risk for patients and should become part of the awareness of all mental health professionals, their patients, and their patients’ families. Furthermore, we shall find that TD brings with it the additional risk of irreversible cognitive dysfunction and dementia (chapter 5).

There is evidence that rates for tardive dyskinesia are increasing. It may be caused by the growing tendency to use drugs with seemingly more toxic effects on the extrapyramidal system, such as Haldol and Prolixin (see Jeste & Wyatt, 1981). These drugs also come in long-acting

40 Neuroleptic Malignant Syndrome and Related Disorders

intramuscular preparations that do not permit patients to independently lower their own dosages by taking fewer pills than prescribed.

It is unusual for TD to develop in less than 3-6 months’ treatment and standard texts suggest that TD which develops earlier requires special investigation. However, it is not possible to place too much emphasis on one point that has been mentioned by Tepper and Haas (1979) and others (for example, Hollister. 1976): tardive dyskinesia can develop in low-dose, short-tenn treatment. DeVeaugh-Geiss (1979) has seen cases develop in a matter of weeks. I have seen several cases develop at around 3 months of treatment. One patient developed tardive dyskinesia after 1 month of recent exposure, with a history of 2 months’ prior exposure several years earlier. One case which developed in 3 months of constant exposure had a probable history of prior head injury from childhood. In the elderly, many cases may develop within a few weeks (see below).

THE ELDERLY AND
OTHER VULNERABLE POPULATIONS

It is important to remember that medications in general are more likely to cause dysfunction in the elderly (Nolan & O’Malley, 1988). Nowhere is this demonstrated more tragically than in regard to TD.

A study of elderly nursing home patients by Yassa, Nastase, Camille, and Belzile (1988) found that 41 % developed tardive dyskinesia over a period of only 24 months and that none fully recovered. While long-term studies have found a spontaneous dyskinesia prevalence of 1%-5% in the elderly, none of the non-drug-treated controls developed spontaneous dyskinesias during the 2 years. Yassa, Iskander, and Ally (1988) found TD in 45% of an outpatient clinic population with a mean age of 60.

In a more recent study, Yassa, Nastase, Dupont, and Thibeau (1992) followed up patients from a geriatric psychiatric unit who had received neuroleptics for the first time during the hospitalization. Out of 99 patients, 35 (35.4%) had developed TD after a mean exposure of 20.7 months. Of these 35, 21 had moderate TD and 3 had severe. Some had tardive dystonia (see below).

Saltz and his colleagues (1991) found the incidence of TD was 31 % following 43 weeks of cumulative neuroleptic treatment in the elderly. The incidence was higher among patients who had previous electroshock

Brain-Disabling Treatments in Psychiatry 41

treatment. Patients with early signs of parkinsonism developed TD at a faster rate. Of great importance, in this older population, the mean cumula- tive time while taking neuroleptics was very brief, a mere 22.7 weeks. One patient developed TD at 2 weeks.

Jeste, Lacro, Gilbert, Kline, and Kline (1993), in an ongoing prospective study, found that 26% of middle-aged and elderly patients developed TD after 12 months. The authors also reviewed the literature on neuroleptic withdrawal and found “that almost 60 percent of the patients withdrawn from neuroleptics did not relapse over a mean period of 6 months.” They concluded, “it seems feasible to discontinue neuroleptic medication from a select population of older schizophrenic patients, if it is done carefully with adequate monitoring and follow up.” They also experimented with brief 2-week placebo-substituted withdrawal in their own group of pa- tients, both younger and older subjects, and found it relatively benign: none relapsed or required resumption of neuroleptics. They concluded, “Given the heightened risk of TD in older patients, it seems that a trial of neuroleptic withdrawal is warranted in this population.”

Jeste et aI. (1993) emphasize that “The potential seriousness of neuro- leptic-induced TD warrants obtaining competent, informed consent to treatment from patients or guardians.” They recommended that consent be periodically renewed and cited other sources to confirm their position.

In addition to age, prior brain damage probably increases the risk of TD (Breggin, 1983; Chouinard, Annable, Ross-Chouinard, & Nestoros, 1979), although studies are contradictory and not conclusive. McKeith, Fairbairn, Perry, Thompson, and Perry (1992) found that 13 of 16 patients with Lewy body type dementia showed deterioration on neuroleptics, including the development of extrapyramidal features. The authors con- clude, “Severe, and often fatal, neuroleptic sensitivity may occur in elderly patients with confusion, dementia, or behavioral disturbance. Its occur- rence may indicate senile dementia of the Lewy body type . . . ” Pourcher, Cohen, Cohen, Baruch, and Bouchard (1993) found a correlation between TD and prior organic brain disorder.

Relapse, Exacerbation, and Delayed Onset after Termination

TD typically waxes and wanes, both in the course of a day and in the course of weeks or months. Especially in the elderly, both partial remissions and relapses are common (Lacro et aI., 1994).

42 Neuroleptic Malignant Syndrome and Related Disorders

As in many neurological disorders, the manifestations ofTD can worsen during stress and can be somewhat calmed with sedation (Jeste & Caligiuri, 1993). In my experience, anxiety, exhaustion, and other general stresses to the mind and body can temporarily exacerbate the symptoms, while relaxation, when possible, can temporarily reduce them.

With great effort, patients can sometimes suppress some of their symp~ toms for a short time. They can also integrate their movements into more natural-looking actions, such as grooming or smiling, in order to disguise them. One patient with whom I consulted would hide her involuntary facial grimaces by trying to smile. The effect was to make her look even more strange to the casual observer.

Neither the fact that TD waxes and wanes, sometimes in response to stress, nor the patient’s ability to partially suppress it with an exertion of will, should mislead observers into believing that it is psychological or emotional in origin. Too often the early signs of TD are overlooked, denied, or dismissed by physicians on these mistaken grounds.

Christensen, Moller, and Faurbye (1970) have documented that a signif- icant percentage of TD cases may not show up at all until many months or even several years after discontinuation of the treatment. They believe that the symptoms are brought on by the interaction between the damage caused by the drugs and by the aging process. If this is true, then a tragic reality may develop as we observe the evolution of TD in aging populations. I have on occasion seen cases that did not become apparent until several months or more after termination of treatment.

Reversibility Is Rare

In the vast majority of cases, TD is irreversible and there is no effective treatment. One repOlt indicates that among patients with persistent TD, followed for a period of 5 years, 82% showed no overall significant change, 11% improved, and 7% became worse (Bergen et aI., 1989).

Another study followed 49 outpatient tardive dyskinesia cases for a mean of 40 weeks (range 1-59 months) after discontinuation of medication (Glazer, Morgenstern, Schooler, Berkman, & Moore, 1990). Many patients showed noticeable improvement in their movements within the ftrst year after stopping neuroleptics, but only 2% showed complete and persistent recovery. The authors conclude, “A major finding of this study is that complete reversal of TD following neuroleptic discontinuation in chroni- cally treated patients was rare.”

44 Neuroleptic Malignant Syndrome and Related Disorders

underestimated. I therefore reviewed the subject in detail. Fortunately, this is no longer necessary, since it is now well-recognized that children are susceptible to TD at rates no less than adults, and that the disorder is often more virulent in children, because it frequently affects the torso, including posture and locomotion (Breggin, 1983a; Gualtieri & Barnhill, 1988; Gualtieri, Quade, Hicks, Mayo, & Schroeder, 1984; Gualtieri, Schroeder, Hicks, & Quade, 1986). A high percentage of neuroleptic- treated children also develop a permanent worsening oftheir emotional and behavioral problems, psychoses, or dementia (see chapter 5). Physicians should not use neuroleptics for behavioral control in children.

TARDIVE DYSTONIA

It is now apparent that there are at least two related variants of TD, tardive dystonia and tardive akathisia. In a 1988 review of tardive dystonia, Burke and Kang found 21 reports describing 131 patients (for reviews, also see Greenberg & Gujavarty, 1985, and Kane & Lieberman, 1992).

Tardive dystonia involves’ ‘sustained involuntary twisting movements, generally slow, which may affect the limbs, trunk, neck, or face” (Burke et al., 1982, p. 1335). The face and neck are by far the most frequently affected areas of the body. Severe deformities of the neck (torticollis) can cause extreme pain and disability. r have seen several cases affecting the orbital muscles of the eyes (blepharospasm) to the degree that the individual’s vision was impaired, requiring botulin injections to paralyze the muscles. I’ve also seen respiratory and abdominal muscles affected in a painful and debilitating manner.

Tardive dystonia can produce cramplike, painful spasms that temporar- ily prevent the individual from carrying out normal activities. Sometimes the spasms are so continuous that the individual is largely disabled. Dam- age to the joint and skeleton system, including fractures, can occur (Burke & Kang, 1988). The pain and muscle tension, as well as the eff01i to compensate for the spasms, can be exhausting and demoralizing.

The torsions can be worsened by other bodily movements, such as attempts to write or to walk. Sometimes they can be relieved by particular movements, such as touching the chin to relieve torticollis or touching the brow to relieve blepharospasm.

Brain-Disabling Treatments in Psychiatry 43 Physician and Patient Denial of TD

Physicians understandably find it painful to face the damaging effects of their treatments. Sometimes it is difficult for them to confront the damage done to patients by other physicians as well. In addition, physicians may consciously seek to protect themselves or their colleagues by failing to acknowledge or to record obvious symptoms of tardive dyskinesia. I have seen many hospital and outpatient records in which obvious, severe cases of tardive dyskinesia have gone either unrecognized or undocumented, sometimes by several physicians in succession. For example, the nurse’s notes may make clear that the patient is in constant motion, yet the doctor’s physical examination or progress notes will give no indication of the disorder. Even official discharge summaries may fail to record TD in patients who have been demonstrating the disorder throughout the period of hospital or clinic treatment. This denial of the obvious is mirrored within the profession itself, which has been very remiss in recognizing or emphasizing the seriousness of the problem (for an analysis of this history, see Breggin, 1983a; Brown & Funk, 1986; Cohen & McCubbin, 1990; Wolf & Brown, 1987).

Psychiatrists sometimes accuse patients of exaggerating their tardive dyskinesia. In reality, most patients tend to deny the existence or severity of their TD. As discussed in detail in chapter 5, patient denial is caused in part by neuroleptic-induced lobotomy effects and in part by denial associated with brain damage. The mutual denial of TD by physician and patient is an aspect of iatrogenic helplessness and denial-the use of brain-disabling treatments in psychiatry to enforce the patient’s denial of both his personal problems and his iatrogenic brain dysfunction and dam- age (chapter 1).

The Size of the Epidemic

It is difficult to determine the total number of TD cases. Van Putten (see Lund, 1989) estimated 400,000-1,000,000 in the United States. My own earlier estimate is higher, ranging in the several millions (Breggin, 1983). It is no exaggeration to call tardive dyskinesia a widespread epidemic and possibly the worst medically induced catastrophe in history.

Children and TD

When I reviewed the subject in 1983, I was among the first to state that the rate and severity of tardive dyskinesia in children was being vastly

Brain-Disabling Treatments in P5ychiatry 45

As Burke and Kang (1988) point out, tardive dystonia can be mistakenly dismissed as a manifestation of hysteria, psychological in origin: “In this regard it is important to realize that dystonia, like many other neurological disorders, can be influenced transiently by suggestion, placebo, or sedation (e.g., during an amobarbital interview) and such maneuvers cannot exclude a true dystonia.” Also, like many other neurological disorders, it can sometimes be partially controlled by extreme exertions of will.

Tardive dystonia can make an individual appear unsympathetic or bizarre, especially to the uninformed observer who equates the facial grimaces or neck distortions with being “crazy.” As in all the drug- induced dyskinesias, the individual may try to cover up for the disorder with additional movements that make the disorder seem voluntary, and therefore not a product of mental illness. The result can be very confusing or distressing to the observer.

TARDIVE AKATHISIA

Tardive akathisia involves a feeling of inner tension or anxiety that drives the individual into restless activity, such as pacing (see chapter 3 for details). The first report of tardive akathisia I have located in the literature was published by Walter Kruse in 1960. He described three cases of muscular restlessness that persisted at least 3 months after discontinuation of treatment with fluphenazine and trit1upromazine. The “akathisic syn- drome … consisted of inability to sit still, pacing the floor all day, jerky movements of arms and shoulders.” Once again Delay and Deniker (1968) were also among the first clinicians to notice the disorder. In discussing “syndromes persisting after cessation of medication,” they mention “hy- perkinetic” ones. As early as 1977, Simpson more definitively made an association between tardive dyskinesia and akathisia that would not re- spond to treatment.

Gualtieri and Sovner (1989) reviewed the subject of tardive akathisia, cited studies with prevalence rates of 13%-18%, and called it “a signifi- cant public health issue.” Nonetheless, the drug companies have ignored it in the labeling of their products.

The anguish associated with akathisia should not be minimized. Con- sider Van Putten’s (1974) description of a mild, temporary akathisia or hyperkinesia: “Patient feels ‘all nerved up,’ ‘squirmy inside,’ ‘uptight,’

46 Neuroleptic Malignant Syndrome and Related Disorders

‘nervous,’ ‘tense,’ ‘uncomfortable,’ ‘impatient’…. Subjective feeling of ill-being may be accompanied by restless changes in posture.”

One reason that so little attention has been given to the mental disruption associated with the dyskinesias is the tendency to blame the mental compo- nent on the mental illness of the patient. Indeed, it has been commonplace to blame the obvious motor disturbances on the mental illness as well, often resulting in increased treatment, and a worsening of the symptoms, until immobility sets in, masking the entire process.

It takes no great imagination to grasp the suffering of a patient con- demned to a relatively mild tardive akathisia for a lifetime. I have seen cases of this kind that were previously mistaken for severe anxiety or agitated depression. Chapter 3 reviewed research indicating that acute akathisia can drive a patient into psychosis, and to violence and/or suicide. Considering the millions of patients subjected to this torment, the problem takes on epidemic proportions.

Tardive akathisia can be subtle. A woman in her mid-sixties consulted me because of seemingly bizarre feelings that other doctors attributed to her depression and to somatic delusions or hallucinations. She had a feeling of “electricity” going in periodic bursts throughout her body. Although she sat quietly in the office, she spoke of feeling fidgety and driven to move about.

Her hospital and clinic charts disclosed that 2 years earlier she had been treated for approximately 6 months with neuroleptics. The sensation she was describing had first been noted while she was taking the medica- tion. I concluded that she probably had tardive akathisia, a subtle case that did not actually force her to move about. However, because she didn’t show external signs of the disorder, other physicians were reluctant to make the diagnosis. The patient felt “driven to distraction” and even to suicide by the disorder; but after my probable diagnosis, she actually felt somewhat relieved. At least she was being taken seriously.

In 1993, Gualtieri wrote:

In telms of clinical treatment and the public health, however, TDAK [tardive akathisia] is a fact, not a question. It is one more serious side effect of neuroleptic treatment, like TD and the Neuroleptic Malignant Syndrome. Taken together, they define neuroleptic treatment as a necessary evil, a treatment that should be administered with care and caution, and reserved for patients who have no other recourse.

Brain-Disabling Treatments in Psychiatry 47 RESPONSES TO TARDIVE DISORDERS

Physical Exhaustion

Fatigue to the point of exhaustion almost always accompanies tardive disorders of any severity. The patient can be exhausted by the movements themselves, by the effort to hide them, and by increased effort required to cany out daily activities. The primary impact on the brain itself may also produce fatigue. Although the disorders tend to disappear in sleep, they can make it difficult to fall asleep, adding to the exhaustion. Having to contend with the physical pain associated with tardive akathisia (inner torment) and \vith tardive dystonia (muscle spasms) can also wear a person down.

Psychological Suffering

Commonly, patients experience shame and humiliation, often leading to social withdrawal. Even a seemingly mild dyskinesia that affects facial expression can be sufficiently humiliating to cause a person to withdraw from society. So can a speech abnormality that makes a person seem to “talk funny.”

The experience of constant pain from dystonia or inner torture from akathisia can drive a person to suicidal despair. The physical disabilities associated with disorders can also become very depressing to patients.

In a clinical report from the Mayo Clinic by Rosenbaum (1979), depres- sion was found closely linked to tardive dyskinesia. Rosenbaum states, “Almost all patients in our series had depressive symptoms accompanying the onset of tardive dyskinesia,” and he cites other studies confirming his observation.

Tardive dyskinesia patients often feel very betrayed by the doctors who prescribed the medication or who later failed to detect the disorder or to tell the patient about it. Too frequently, perhaps in a self-protective stance toward their colleagues, several psychiatrists in a row will fail to inform the patient or family about the obvious iatrogenic disorder. This can leave patients feeling that they cannot trust psychiatrists. In the extreme, it can create an understandable distrust of doctors in general.

Even a slight or minimal de!,’Tee of tardive disorder can end up seriously impairing an individual’s quality of life.

48 Neuroleptic Malignant Syndrome and Related Disorders

NEUROLEPTIC \VITHDRAWAL SYNDROME

Withdrawal frequently causes a worsening mental state. including tension and anxiety. With those drugs that produce potent anticholinergic effects. such as Thorazine and MeHaril, a cholinergic withdrawal syndrome (cho- linergic rebound) may develop that mimics the flu, including emotional upset, insomnia, nausea and vomiting, diarrhea, anorexia and weight loss, and muscle aches.

Withdrawal symptoms can also include a temporary worsening of dyski- netic effects, both painful and frightening.

While classic addiction to these substances has not been demonstrated, the drugs should be considered addictive in the sense that withdrawal symptoms can make it impossible for patients to stop taking them. For this reason, I have suggested viewing these drugs as addictive (Breggin, 1989a, 1989b).

Because of the withdrawal symptoms, it is often necessary to reduce these drugs at a very slow rate. Sometimes withdrawal seems to be impossible. I have described the principles of withdrawing from psychiat- ric drugs in Talking Back to Prozac.

NEUROLEPTIC-INDUCED PSYCHOSIS AND DEMENTIA

The following chapter will describe irreversible psychosis and dementia associated with the neuroleptics. These may first become obvious as withdrawal effects that make it seemingly impossible to stop the drug therapy.

OTHER NEUROLEPTIC-INDUCED NEUROLOGICAL IMPAIRMENTS

The neuroleptics can produce a variety of other symptoms of central nervous system dysfunction, including abnormal electroencephalogram (EEG) findings, an increased frequency of seizures, respiratory depression, and disturbances of body temperature control (Davis, 1980; Davis & Cole,

Brain-Disabling Treatments in Psychiatry 49

1975). Endocrine disorders, especially in females, may also be of central nervous system origin (Davis, 1980). There is some evidence that auto- nomic dysfunction can become irreversible (tardive autonomic disorders).

NEUROLEPTIC MALIGNANT SYNDROME (NMS)

This devastating disorder was seemingly so bizarre, unexpected, and inex- plicable that physicians for years literally refused to believe their eyes. Seven years after the introduction of the drugs into North America, Leo Hollister (1961) reviewed their side effects for “Medical Intelligence” in the New England Journal of Medicine. In two separate places, he referred to syndromes that probably were NMS. He described a “bizarre” dystonic syndrome that can b e ‘ ‘confused with hysteria, tetanus, encephali- tis or other acute nervous-system disorders; a rare fatality may occur.” Later he mentioned that “other clinical syndromes attributed to central- nervous-system effects of these drugs have resembled acute encephalitis, myasthenia gravis, bulbar palsy or pseudotabes.”

Although NMS was identified in an English-language publication by Delay and Deniker as early as 1968, physicians continued to be reluctant to recognize the syndrome. Delay and Deniker declared it was caused by the neuroleptics, specifically including haloperidol (Haldol) and t1uphen- azine (Prolixin). Any neuroleptic can cause NMS. However, clinicians have found an increased danger with long-acting injectable neuroleptics.

Delay and Deniker were already able to identify many of the compo- nents of NMS, including pallor, hyperthermia, a severe psychomotor syndrome with akinesia and stupor or hypertonicity with varying dyskine- sias. They warn that, at the first suspicion, “one must stop medication immediately and completely.” They were already aware of fatalities. That the syndrome was named and definitively identified in English in 1968 is most remarkable in light of the failure of drug companies to give it formal recognition until compelled to do so by the FDA almost 20 years later (see chapter 11 for further discussion).

Neuroleptic malignant syndrome is characterized by “such symptoms as severe dyskinesia or akinesia, temperature elevation, tachycardia, blood pressure t1uctuations, diaphoresis, dyspnea, dysphagia, and urinary incon- tinence” (Coons, Hillman, & Marshall, 1982). If unrecognized, as too often happens, it can be fatal in morc than 20% of cases. The syndrome

50 Neuroleptic Malignant Syndrome and Related Disorders

frequently leaves the patient with permanent dyskinesias and dementia (see chapter 5).

Most cases develop within the first few weeks of treatment (even within 45 minutes!), but some develop after months or years, or after increased dosage (Gratz, Levinson, & Simpson, 1992).

Estimates for rates of neuroleptic malignant syndrome vary widely but studies indicate that they are very high. Pope, Keck, and McElroy (1986) surveyed 500 patients admitted during a I-year period to a large psychiatric hospital and found a rate of 1.4%. The cumulative rate for patients would be much higher. Addonizio, Susman, and Roth (1986) carried out a retro- spective review of 82 charts of male inpatients and found that prevalence for the diagnosed syndrome was 2.4%. Again, the cumulative rate over repeated hospitalizations or years of treatment would be much higher.

Although it is sometimes called’ ‘rare,” NMS should be described as common or frequent 0/100 is common by FDA standards).

The rates for neuroleptic malignant syndrome, as well as its potential severity and lethality, make it an extreme risk for patients receiving antipsychotic drugs. A risk of this size would probably result in most drugs in general medicine being removed from the market.

I have reviewed cases in which several physicians at a time missed making the correct diagnosis in what seemed, from my retrospective analysis, like an obvious case of NMS. The failure to stop the neuroleptic and to institute proper treatment resulted in severe, permanent impair- ments, or death. The mistaken idea that NMS is rare may contribute to these errors in judgment.

After reviewing episodes of NMS in 20 patients, Rosebush and Stewart (1989) found that most cases fit the following cluster of symptoms: delir- ium, a high fever with diaphoresis, unstable cardiovascular signs, an elevated respiratory rate, and an array of dyskinesias, including tremors, rigidity, dystonia, and chorea.

Patients spoke little during the acute illness and later reported that they had found themselves unable to express their anxiety and feelings of doom. Almost all patients were agitated shOltly before developing NMS, suggesting to the authors that they were undergoing akathisia. The white blood cell count was elevated in all cases, dehydration was common, and lab tests showed a broad spectrum of enzymatic abnormalities, including indications of muscle breakdown.

There is little or nothing about acute NMS to distinguish it from an acute, severe episode of encephalitis, especially lethargic encephalitis

Brain-Disabling Treatments in Psychiatry 51

(also called von Economo’s disease), except for the fact of exposure to neuroleptic therapy. I have previously compared neuroleptic toxicity and lethargic encephalitis in detail (Breggin, 1993; also see chapter 5).

Although Rosebush and Stewart provide insufficient data to draw exact parallels, their NMS patients also suffered chronic impairments similar to those reported in lethargic encephalitis patients. Of the 20 patients, 14 continued to have “extrapyramidal symptoms or mild abnormalities of vitals signs and muscle enzymes at the time of discharge” (p. 721); but we are not told how many of the 14 specifically had persistent extrapyrami- dal signs. In a striking parallel with lethargic encephalitis, three patients displayed persistent parkinsonian symptoms until they were lost to follow- up. One patient, who had mild cognitive impairment prior to NMS, devel- oped a persistent worsening of her dementia.

Neuroleptic malignant syndrome has also been reported with the atypi- cal neuroleptics, clozapine (Anderson & Powers, 1991; DasGupta & Young, 1991) and risperidone (Dave, 1995; Mahendra, 1995; Raitasuo, Vataga, & Elomaa, 1994; Singer, Colette, & Boland, 1995).

NEUROLOGICAL MECHANISMS OF PARKINSONISM AND TD

Drug-induced parkinsonism apparently develops in part, but not wholly, from blockade of dopamine receptors in the basal ganglia, specifically the striatal region or striatum (the caudate and putamen), producing motor retardation, rigidity, and other symptoms. Damage and degeneration in the pigmented neurons of the substantia nigra play a key role. These neurons terminate in the striatum, where, when they are functioning nor- mally, they release dopamine to act on striatal dopamine receptors.

Tardive dyskinesia is a more delayed reaction, probably based on the development of reactive supersensitivity or hyperactivity in these same striatal dopamine receptors following continuous blockade (see American Psychiatric Association, 1980; Fann, Smith, Davis, & Domino, 1980; Klawans, 1973; and chapter 5 in this volume). This supersensitivity of the dopamine receptors becomes most obvious when the drug is reduced or eliminated, terminating the blockade. The overactive, unblocked receptors produce the tardive dyskinesia symptoms. Undoubtedly a great deal more must be learned about the neuropathology of both these drug-induced

52 Neuroleptic Malignant Syndrome and Related Disorders

diseases, which probably involve multiple neurotransmitter system abnor- malities.

CONCLUSION

The widespread use of neuroleptics has unleashed an epidemic of neuro- logic disease on the world. Even if tardive dyskinesia were the only permanent disability produced by these drugs, this would be among the worst medically induced disasters in history. Meltzer (1995) has urged that attempts be made to remove long-term patients from neuroleptics and has attempted to demonstrate its feasibility. Gualtieri (1993), warning about the extreme dangers, has suggested neuroleptics be viewed as a therapy of last resort. I believe the profession should make every possible effort to avoid prescribing them. Although beyond the scope of this book, it is worth ending with a reminder that there is strong evidence that psychosocial alternatives can be more effective in the treatment of both acute and chronic patients labeled schizophrenic (Breggin, 1991a; Breg- gin& Stern, 1996; Karon & Vandenbos, 1981; McCready, 1995; Mosher & Burti, 1989).

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