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1 Cure Or Curse: What Are Antipsychotics? 3 Magic Bullets Notes 1 Cure or Curse: What Are Antipsychotics? 1. Receptors are chemicals on the outside of brain cells to which neurotransmit- ters attach and through which they effect their actions. 2. Laing’s precise phrasing was ‘a perfectly rational adjustment to an insane world’. 3 Magic Bullets: The Development of Ideas on Drug Action 1. I am indebted to other accounts that have noted how a disease-centred view of antipsychotic action emerged during the 1950s and 1960s, especially those of David Healy, Robert Whitaker and Sheldon Gelman (Gelman, 1999; Healy, 2002; Whitaker, 2002). 2. The ‘extrapyramidal’ system denotes the brain centres responsible for the involuntary control and regulation of movement, and is so named to contrast with the ‘pyramidal’ system, which is a pyramid-shaped tract of nerves that is directly involved in voluntary movement. 4 Building a House of Cards: The Dopamine Theory of Schizophrenia and Drug Action 1. The technique involves the injection of a radioactively-labelled chemical called a ‘ligand’ that binds to the receptor site; the positrons emitted by the ligand are detected by the radioactivity scanner. 5 The Phoenix Rises: From Tardive Dyskinesia to the Introduction of the ‘Atypicals’ 1. I am indebted to other accounts of the emergence of tardive dyskinesia (Tarsy, 1983; Breggin, 1993; Gelman, 1999). 2. The term ‘tardive dyskinesia’ literally means late-onset (tardive) abnormal movement (dyskinesia). 3. The basal ganglia is a group of nerve cell nuclei located below the cerebral hemispheres, which form part of the extrapyramidal system. They include the striatum (the name for the caudate nucleus and the putamen), and are sometimes referred to as the striatum or striatal system. 8 Chemical Cosh: Antipsychotics and Chemical Restraint 1. The Mindfreedom and Psychrights organisations have organised demonstra- tions against forced drugging in the USA; the Kissit campaign and Beyond 221 222 Notes Bedlam have been active in the UK, Mad Pride in Eire and We Shall Overcome in Norway. 2. I am grateful to Dr Laura Allison who undertook some of the research for this chapter during the course of her studies for an MSc in Psychiatric Research at University College London. 3. Hydrotherapy involved prolonged immersion in cold or hot baths and was practised in asylums from the late nineteenth century. 4. Under Section 41 of the Mental Health Act of England and Wales people who have committed serious offences are made subject to government supervision after discharge from hospital. 9 Old and New Drug-Induced Problems 1. The brain consists of grey matter, which comprises the nerve cell bodies, and white matter, which consists of the projecting and connecting fibres. 2. The cerebral hemispheres (also known as the cerebral cortex) are the largest part of the brain and responsible for higher intellectual abilities. 3. These overall differences between patients and controls were not provided in the paper, but could be calculated from other data provided. 4. A transient ischaemic attack (TIA) occurs when there is a temporary loss of blood supply to part of the brain causing a temporary neurological deficit. 10 The First Tentacles: The ‘Early Intervention in Psychosis’ Movement 1. Schizotypal personality disorder is defined as ‘a pervasive pattern of social and interpersonal deficits marked by acute discomfort with, and reduced capacity for, close relationships, as well as by cognitive and perceptual distor- tions or eccentricities of behaviour beginning in early adulthood and present in a variety of contexts’ (American Psychiatric Association, 1980a). 12 All is not as it Seems 1. ‘Tolerance’ is a pharmacological term referring to the phenomena in which the body produces alterations that help to combat the effects of a drug when it is taken on an on-going basis. 2. The quotation cited is from one of two articles that Spitzer wrote in response to the famous Rosenhan experiment, in which psychology students posed as potential patients by presenting at accident and emergency departments saying they heard a voice saying ‘thud’. All were admitted as psychiatric inpatients and discharged with a diagnosis of schizophrenia or schizophrenia ‘in remission’. The experiment sparked accusations that psychiatrists could not distinguish the mad from the sane, and added to other criticisms of the reliability and validity of psychiatric diagnosis (Rosenhan, 1973). 3. The Soteria Network, for example, is a group of professionals, patients and carers interested in developing alternative services for those with severe mental disor- ders in the UK. The network supports small independent initiatives, as well as working with mainstream services (http://www.soterianetwork.org.uk/). Appendix 1: Common Antipsychotic Drugs Approximate Chemical class Principle or original year of manufacturer introduction into UK First generation, oral antipsychotics Chlorpromazine 1954 Phenothiazine (aliphatic side chain) Rhône-Poulenc (now (Largactil, Thorazine) Sanofi Aventis) and Smith Kline & French 223 (now GlaxoSmithKline) Droperidol (Droleptan) 1980 Butyrophenone Janssen Withdrawn in UK in 2001 Flupentixol (Depixol) 1970s Thioxanthene Lundbeck Fluphenazine 1970s Phenothiazine with piperazine side chain Sanofi Aventis Haloperidol (Haldol, 1958 Butyrophenone Janssen Serenace) Perphenazine 1957 Phenothiazine with piperazine side chain Allen & Hanburys (Fentazin) (absorbed by Glaxo in 1958) Sulpiride (Dolmatil) 1983 Benzamide Sanofi Aventis Thioridazine (Melleril) 1960 Phenothiazine with piperidine side chain Sandoz (now Novartis) Withdrawn in UK in 2005 Trifluoperazine 1958 Phenothiazine with piperazine side chain Smith Kline & French (Stelazine) (continued) 224 Appendix 1 Continued Approximate Chemical class Principle or original year of manufacturer introduction into UK Zuclopenthixol 1962 Thioxanthene Lundbeck (Clopixol) First-generation, long-acting injectable antipsychotics Flupentixol decanoate 1972 Thioxanthene Lundbeck (Depixol) Fluphenazine decanoate 1968 Phenothiazine with piperazine side chain Sanofi Aventis (Modecate) Haloperidol (Haldol) 1982 Butyrophenone Janssen Pipotiazine palmitate 1983 Phenothiazine Sanofi Aventis (Piportil) Zuclopenthixol 1978 Thioxanthene Lundbeck decanoate (Clopixol) Second-generation oral antipsychotics Amisulpride (Solian) 1997 Benzamide Sanofi Aventis Aripiprazole (Abilify) 2004 Quinalone Bristol-Myers Squibb Clozapine (Clozaril) 1990 Tricyclic dibenzodiazepine Novartis Olanzapine (Zyprexa) 1996 Thienobenzodiazepine Eli Lilly & Co. Quetiapine (Seroquel) 1997 Dibenzothiazepine AstraZeneca Risperidone (Risperdal) 1993 Benzisoxazole Janssen Zisprazidone (Geodon) Not licenced Pfizer in UK; licenced in US in 2001 Second-generation long-acting, injectable antipsychotics Olanzapine embonate 2008 Thienobenzodiazepine Eli Lilly (ZypAdhera) Paliperidone 2011 Benzisoxazole Janssen palmitate (Xeplion) Risperidone (Risperdal 2002 Benzisoxazole Janssen Consta) 225 Appendix 2: Accounts of Schizophrenia and Psychosis The following three accounts are abridged versions of stories found in the National Institute for Health and Clinical Excellence’s (NICE) guideline on the treatment of schizophrenia (National Institute for Health and Clinical Excellence, 2002). Story 1 Mr A described how he started to develop symptoms while he was at University. He was hearing voices and ‘reading strange meanings into what was going on’. He was referred to a psychiatrist, but managed to persuade the psychiatrist that there was nothing wrong, and he recovered without any intervention and went on to finish his degree. Later, in his mid-20s, while he was working as a research scientist, he started to hear voices and also to see things, and he was hospitalised after he took an overdose triggered by his dis- tress at what was happening. He was started on an antipsychotic drug in hos- pital, which he describes as the start of a ‘vicious cycle’. He would be put on drugs, find it difficult to function at work, stop taking them and end up being readmitted to hospital. Eventually, he had to give up work, and after 20 years, and despite being on antipsychotic treatment, he describes how the ‘voices are still awful when they are really loud. They discuss me, put me down, shout obscenities, comment on what is happening to me and tell me to do things that put me in danger. It is very difficult to remain communicating in the real world, and doing this leaves me exhausted. In addition, I often end up seeing the world in a very different and frightening way and at the time I’m having these delusions I really believe them. I can still get very distressed by it all but these days living with schizophrenia is easier than it was when I was first ill’. Story 2 Mr B developed symptoms at the age of 33 years. He felt ‘wonderfully excited as though I was the only person in the country to be let in on a great secret’ and recounted how he spent the summer travelling around in search of more ‘delusional excitement’, and thought he had ‘become involved in the peace process in Northern Ireland’. At the end of the summer he was admitted to hospital after an outburst in which he caused a considerable amount of dam- age to property. In hospital he was prescribed an antipsychotic, which made him ‘suicidally depressed’ and he stopped taking it as soon as he was dis- charged. He spent the next 10 years in a cycle of ‘gradually getting ill’, which he usually enjoyed, ‘getting arrested, being sectioned, and feeling suicidal because of the side effects of the drugs’. At the time he said his ‘benchmark
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