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Schizophrenia Handbook

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Schizophreniahandbook

H. Lundbeck A/S 9 Ottiliavej DK - 2500 Valby Copenhagen, Denmark Tel: +45 36 30 13 11 Fax: +45 36 43 89 00 www.lundbeck.com September 2006

This booklet is sponsored by H. Lundbeck A/S an international pharmaceutical company engaged in the research and development, production, marketing and sale of drugs for the treatment of psychiatric and neurological disorders.

Contents

Page Foreword What is schizophrenia? What is the frequency of schizophrenia? What causes schizophrenia? How is schizophrenia diagnosed? What are the signs and symptoms of schizophrenia? How is schizophrenia treated? What are the co-morbidities of schizophrenia? What is the social and economic impact of schizophrenia? Further information sources Abbreviations and glossary Index 1 3 9 11 15 19 23 29

31 35 37 41

Foreword

Even now in the 21st Century, mental illnesses, such as schizophrenia, remain misunderstood, poorly diagnosed, and under-treated. Despite the advances in medical therapies available for this disorder over recent decades, there are still many unmet needs in schizophrenia therapy and we still do not understand the disorder fully.The first major advance for patients, families, carers and physicians alike, would be treatments with increased effectiveness against all subtypes of symptoms, accompanied by fewer side effects. These medications would also have a rapid action with positive effects on the conditions that frequently occur alongside schizophrenia, such as those involving cognition and mood. In addition, there is still a significant group of patients who do not respond to existing therapies, and we should not give up on research to find new treatments which may be effective for these patients. But medication is not the only improvement needed in the therapy for this disorder. Earlier diagnosis would also be helpful, as would better follow-up and more accessible and consistent community care.

Improved communication between the patient, family and physician and the active engagement of families and carers in the treatment and care model are other issues which need to be tackled. Research is ongoing in all these areas, looking at new treatments and healthcare approaches, whilst maintaining the ultimate aims of discovering a cause for the disorder and a cure. In the meantime, education to raise awareness and decrease stigma are other valuable ways to improve the lives of those with schizophrenia. This booklet has been designed as a short synopsis of schizophrenia to provide you with more information on the disorder.

Inger Nilsson, President of EUFAMI

European Federation of Associations of Families of People with Mental Illness1

Foreword

2

What is schizophrenia?What is schizophrenia?3

Schizophrenia is the most common form of severe mental illness,1 affecting approximately 24 million people worldwide.2 It is believed to be caused by an imbalance of chemicals in the brain (neurotransmitters), and is characterised by psychotic episodes (delusions, hallucinations, disorganised behaviour) interspersed with periods of blunted emotions, apathy, and withdrawal. However, although the condition is highly treatable, it is complex and poorly understood, and the word schizophrenia is associated with notable stigma and is often misused. A person with schizophrenia experiences a condition where their thoughts (cognition), emotion, and behaviour become disturbed and they may find it difficult to judge reality. These underlying processes produce symptoms that are highly variable, but typically include hallucinations, delusions, apathy, blunted emotions, odd behaviour, poor personal care, and social withdrawal. Consequently, schizophrenia affects most aspects of the human condition, and the resulting symptoms can appear strange and frightening for both the patient and those around them.

Although mental disorders have been studied and described since medical records began, it was the German psychiatrist, Emil Kraepelin (18561926), who first classified mental illness as an actual disease with a specific onset, course and outcome. As part of this classification, Kraepelin described the condition dementia praecox, meaning early mental decline. Dementia praecox was later renamed schizophrenia following extensive study of the symptoms of the disorder by the Swiss psychiatrist, Eugen Bleuler (18571939). The name schizophrenia (from the Greek: schizo=split, phrenos=mind) was chosen to reflect the poor connection between the thought processes (cognition) of a person with the disorder, and other functions of the mind such as emotion, behaviour, and volition (self-will). It is a common misconception that patients with schizophrenia exhibit a split or multiple personality.

Images courtesy of Max Planck Institute and www.corbis.com.

Emil Kraepelin (18561926)

Eugen Bleuler (18571939)

The course of schizophreniaThe pattern of symptoms and psychotic episodes in schizophrenia varies from person to person (Figure 1). In addition, schizophrenia can also change over time, with different types of symptoms becoming predominant.3 In general, the course of the disorder is long-term

(chronic), consisting of recurrent short-term (acute) episodes characterised by high levels of psychotic symptoms with longer periods with less pronounced psychotic symptoms, or sometimes recovery, in between. Other symptoms, such as negative and cognitive symptoms, are often present in both stages of the disorder.

Figure 1: Patterns in the development and course of schizophrenia

Onset Aacute

Courseepisodic

Outcomemild or recovered

% with this pattern

25

B

acute

continuous

moderate or severe

8

C

gradual

episodic

mild or recovered

10

D

gradual

continuous

mild or recovered

10

E

gradual

continuous

moderate or severe

24

F4

other patterns

23

Adapted from: Target schizophrenia. The Association of the British Pharmaceutical Industry, London, 2003.1

The onset of symptoms can be sudden, or may be preceded by weeks, months or years of gradually increasing symptoms, known as the prodromal phase. Prodromal signs tend to be non-specific and can include patterns of social isolation, neglected personal hygiene, loss of interest in work/study, and development of odd behaviour and ideas. The psychotic episode is characterised by more so-called positive symptoms, where an individual may experience delusions, hallucinations, fear/anxiety, and may lose the perception of reality. With treatment or, in some cases, left untreated, the active phase diminishes, leaving the person functional again (in remission), or with varying severities of negative and/or cognitive symptoms. These symptoms include blunted emotions, lack of drive/interest,

problems with planning or abstract thinking, and a tendency towards isolation. This period of successful treatment is known as the maintenance phase. After the first psychotic episode, the course of the disorder is unpredictable. As many as 15% of people who experience an acute episode of schizophrenia will never have another episode and recover completely.4 However, more commonly, the person will relapse into further active phases interspersed with residual phases.4 Complete remission (recovery) is less likely once a long-term pattern of episodes becomes established. In addition, 50% of patients with schizophrenia attempt suicide at some point during the course of the disorder, leading to fatality in 10% of cases.1 The overall mortality rate is considerably higher in people with schizophrenia than in the general population (due to coexisting medical problems, as well as suicide).

First visit to a doctor Mrs Johnson requested an appointment with her general practitioner to speak about her son, James, who was aged 18. James was a physically fit young man, but in recent months his behaviour had started to become unusual. He had lost interest in socialising or contacting his friends, and was unresponsive to any attempt at conversation occasionally muttering inaudible or cryptic phrases. He would spend most of his time withdrawn in his room, talking as if he was conversing with some other unseen person. Upon meeting James, the doctor was unable to extract any coherent responses to his questions, and referred him to a psychiatrist for further diagnosis.5

Who is affected?Schizophrenia is most common in young adults, with the majority of individuals developing the disorder between the ages of 15 and 25 years.5 Onset is rare beyond age 40, but it is possible for schizophrenia to develop at any time of life. Schizophrenia affects men and women in approximately equal numbers. However, men tend to develop the disorder 35 years earlier than women (Figure 2). There is also evidence to suggest that, in general, men experience more severe symptoms than women, although women appear to have a worsening of symptoms during the menopause. Schizophrenia affects all cultures.5 Well-known individuals with schizophrenia have included Vaclav Nijinsky (ballet dancer/choreographer), Syd Barrett (musician, Pink Floyd), Peter Green (musician, Fleetwood Mac), and Eduard Einstein (son of physicist, Albert). Schizophrenia has also been portrayed on film, in the life stories of John Nash (mathematician/Nobel prize winner A beautiful mind) and David Helpffgott (pianist Shine), and in the fictional account of One flew over the cuckoos nest.

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Figure 2: Relative risk of the onset of schizophrenia versus age

Incidence of schizophrenia

Female Male

Median 25 years 20 25

Median 28 years 30 Age (years) 35 40 45

Adapted from: Target schizophrenia. The Association of the British Pharmaceutical Industry, London, 2003.1

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The consequences of schizophreniaAs a diverse and serious condition, schizophrenia produces complex consequences. The obvious major consequence is to the patients themselves, who typically experience severe anxiety and fear during psychotic episodes, prompted by hallucinations, delusions and general loss of reality. While it is distressing for the patient to cope with situations that they genuinely perceive as real, it is also extremely disturbing for family and friends to deal with this often alarming change in behaviour. For every person with schizophrenia, around 10 others are affected by its consequences.1 This can put a strain on relationships, leading to inevitably difficult decisions about care provision, and adding to the general stress of the situation. Aside from emotional concerns, schizophrenia can also impact on an individuals future in terms of education, employment and resulting financial security. The intermittent and unpredictable nature of symptoms makes steady work and independent living difficult for most individuals. Therefore, information and support are necessary for patients and their families to provide adequate patient care and avoid potential decline into problems such as family breakdown, drug and alcohol abuse, and homelessness. As a result, healthcare costs for8

support to patients with schizophrenia are high and wide ranging, with only 1% of the cost of care due to drug treatment. Community followup of hospital treatment is essential for many reasons, not least because one of the highest risk periods for patient suicide is in the first 6 weeks after discharge from hospital following the initial psychotic episode. All these difficulties, combined with the social stigma of this often misunderstood condition can compound the issues facing people with schizophrenia and further impair their chances of regaining their quality of life.

References1. ABPI. Target schizophrenia. May, 2003. 2. World Health Organization (WHO). Schizophrenia. www.who.int/mental_health/ management/schizophrenia, accessed March 2006. 3. Marneros A, Deister A, Rohde A. Validity of the negative/positive dichotomy for schizophrenic disorders under long-term conditions. Schizophr Res 1992; 7 (2): 117123. 4. Watt DC, Katz K, Shepherd M. The natural history of schizophrenia: a 5-year prospective follow-up of a representative sample of schizophrenics by means of a standardized clinical and social assessment. Psychol Med 1983; 13 (3): 663670. 5. NHS National electronic Library for Health. www.nelmh.org/home_schizophrenic.asp?c=10, accessed March 2006.

What is the frequency of schizophrenia?

Schizophrenia most frequently appears in young adults (generally between 15 and 25). Although men and women are affected equally, symptoms may appear later in women than men (see Figure 2, page 7).1 Schizophrenia is a fairly common illness, although estimates of its frequency are variable due to worldwide differences in diagnosis, methods of estimation, and healthcare provision. Data from various studies give a prevalence rate (total number of cases in the population) of about 0.5%. That is, schizophrenia affects 1 in every 200 people worldwide.2 However, the prevalence varies with age, increasing until age 40, and then declining. The estimate of lifetime risk is 1% (or 1 in 100 people). This measure is thought to be a more representative value as it takes into account that the most high-risk age group is between 20 and 39 years.2 Studies of the number of new cases of schizophrenia gave an incidence of 21.8 per 100,000 people.2 This gives an incidence rate of 0.02%. The incidence rate is lower than the prevalence rate because schizophrenia is a predominantly chronic disorder, and so its presence in the population is cumulative.3

Where in the world?The prevalence of schizophrenia does not follow a geographical pattern, appearing to be generally constant across all areas of the world.2 However, there are some variations within individual countries, with a higher number of cases generally found in larger cities. Unfortunately, although the prevalence of schizophrenia shows a relatively constant worldwide distribution, treatment levels do not. The World Health Organization (WHO) estimates that 90% of people with untreated schizophrenia are in developing countries.3

References1. ABPI. Target schizophrenia. May, 2003. 2. Tsuang MT, Faraone SV. Schizophrenia, the facts. Second edition. Oxford University Press, 1997. 3. World Health Organization (WHO). Schizophrenia. www.who.int/mental_health/ management/schizophrenia, accessed March 2006.

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Frequency

10

What causes schizophrenia?

The exact cause of schizophrenia is not yet known, although studies point towards a combination of genetic and environmental factors that influence the function of the brain.

Figure 3: Altered brain activity in patients with schizophrenia

The disorder processThe symptoms of schizophrenia are associated with changes in brain activity, which can be seen using medical imaging techniques that measure electrical activity, as shown in Figure 3. The specific processes of the disorder that cause these changes remain unclear, but one accepted theory is that people with schizophrenia have an imbalance in the chemicals that send signals in the brain (neurotransmitters). For example, visual hallucinations may be due to over-stimulation of certain brain areas by the neurotransmitter, dopamine,1 while the negative symptoms may be correlated with lowered dopamine activity in other brain regions. In addition, brain scans of people with schizophrenia have shown that fluid-filled areas of the brain called the ventricles may be enlarged in some types of schizophrenia, with the amygdala and hippocampus reduced in size (Figure 4).2 How these alterations are connected to the symptoms of schizophrenia is unknown.

Coloured positron emission tomography (PET) scans of axial sections through a healthy brain (left) and a schizophrenic brain (right). The colours show different levels of activity within the brain during an attention test. Red shows high activity, through yellow and green to black (very low activity). The schizophrenic brain shows much lower activity in the frontal lobes.Image from the Science Photo Library.

11

Causes

Figure 4: Areas of the brain in some types of schizophrenia, the ventricles may be enlarged, whilst the amygdala and hippocampus may be reduced in sizea) Brain ventricles and the central canal

Lateral ventricles Third ventricle

Fourth ventricle

Central canal

b) The limbic system

Anterior nucleus of thalmus Corpus callosum Mammillary body of hypothalamus

Area of thalamus (dotted)

Hippocampus

Amygdala

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Is the condition inherited?The parents or siblings of a person with schizophrenia have a 10-fold higher risk of developing the disorder than a person in the general population, and this rises to a 15-fold higher risk for the children of people with schizophrenia (Figure 5).3 However, studies in identical and non-identical twins have shown that development of the condition is not entirely explained by genetic inheritance. In those cases where one identical twin developed schizophrenia, the second identical twin (who would have inherited exactly the same genes) developed schizophrenia in only around 50% of cases.3 The conclusion is that genes (probably a complex interaction of several) do play an important part in whether or not an individual will develop schizophrenia, but that other factors must also play a significant role.

Figure 5: Family patterns of schizophrenia developmentAffected relative None

Cousin

Aunt or uncle

Grandparent

Brother or sister

Parent Non-identical twin

Identical twin 0 10 20 30 40 50 Risk of developing schizophrenia (%)Adapted from: Target schizophrenia. The Association of the British Pharmaceutical Industry, London, 2003.4

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Can the environment be a risk factor?In the nature versus nurture argument, if genes (nature) do not cause schizophrenia every time (as shown by the twin studies), then the environment (nurture), must also be involved in some way perhaps acting as a trigger for the genetic factors. Male gender and winter birth are known to be connected with earlier development of, and higher rates of schizophrenia, respectively. But the mechanism underlying these links is unknown.2 Long-term use of drugs (in particular, use of cannabis and stimulants) is thought to carry increased risk, alcohol may also alter the brain chemistry to produce schizophrenia.5 Other proposed environmental triggers include stress, viral infection, exposure to toxins, physical injury (prenatal or in childhood), or difficult family dynamics, but the connection between these factors and schizophrenia is less well established. References1. Kandel ER, Schwartz JH, Jessell TM. Principles of neural science. Fourth edition. McGraw Hill, 2000. 2. Frith C, Johnstone E. Schizophrenia. A very short introduction. Oxford University Press, 2003. 3. Tsuang MT, Faraone SV. Schizophrenia, the facts. Second edition. Oxford University Press, 1997. 4. ABPI. Target schizophrenia. May, 2003. 5. NHS National electronic Library for Health. www.nelmh.org/home_schizophrenic.asp?c=10, accessed March 2006.

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How is schizophrenia diagnosed?

Schizophrenia is a complex disorder to diagnose due to the variation in symptoms and the lack of a defect measurable by a laboratory or clinical method. Therefore, schizophrenia is generally diagnosed by a psychiatrist, speaking to the patient about their experiences of the condition. The specialist will also aim to establish how long the symptoms have been present, how they are affecting everyday life, and will try to speak to the patients family and friends. It may not be possible to diagnose schizophrenia at an early stage if the symptoms are mild and non-specific, and some physicians may be unwilling to offer a definite early diagnosis due to the immediate social and personal consequences of being labelled with schizophrenia.

DiagnosisThere are two main sets of clinical guidelines that provide standard rules for the diagnosis of schizophrenia. These are: International Classification of Diseases, 10th edition (ICD-10), which is issued by the World Health Organization and is frequently used in Europe1 Diagnostic and Statistical Manual, 4th edition (DSM-IV), which is issued by the American Psychiatric Association and is more frequently used as a guide in the US.2 These classification systems outline the requirements for diagnosis. The first of these is a combination of core symptoms, such as hallucinations, delusions, and disruption in thought processes, along with evidence of functional decline (work, social, self-care). In addition, these symptoms must have been present for a particular duration, which ranges from 16 months, depending on the scale used. Finally, the patient must display no exclusion criteria, that is, the physician must ensure that the symptoms are not being caused by another condition, e.g., drug-use, brain tumour, epilepsy, or mood disorder. In this way, the physician can make a differential diagnosis of schizophrenia.

15

Diagnosis

Differentiating schizophrenia from other disordersSeveral other conditions may produce symptoms that are very similar to those observed in schizophrenia. For effective management, it is extremely important that schizophrenia is differentiated from these other conditions, some of which are described in the table opposite.

Schizoaffective disorderSome patients show equal measures of symptoms of both mood-based (affective) disorders and schizophrenia. In such cases, a schizoaffective disorder may be diagnosed, although it has not yet been established whether these are entirely separate conditions, or different extremes of the same disorder.3

References1. World Health Organization. The ICD-10 classification of mental and behavioural disorders. Diagnostic criteria for research. Geneva, Switzerland. World Health Organization, 1992. 2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Fourth edition. Washington, USA American Psychiatric Association, 1994. 3. Tsuang MT, Faraone SV. Schizophrenia, the facts. Second edition. Oxford University Press, 1997.

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Table 1: Disorders producing similar symptoms to schizophreniaCondition type Drug-induced Examples Known use of drugs such as LSD, cannabis, amphetamines, cocaine, ecstasy. Alcohol abuse. Differentiating factors Symptoms subside upon withdrawal of the drug/alcohol. Note that, long-term abuse of these substances can lead to permanent brain changes that may induce schizophrenia. Brain scans or analysis of cerebrospinal fluid (CSF) show evidence of a distinct physical cause.

Physical

Viral infection of the brain (encephalitis), epilepsy, brain injury, loss of brain cells in old age, brain tumour. Non-brain related impairments in thyroid, liver or kidney function, or diabetes.

Similarly, physical analysis of the blood and organ function (kidney, liver, etc.), will highlight any other causes. Like schizophrenia, they have no known defect that can be confirmed by physical examination. Instead, careful observation of symptoms is required. In contrast to schizophrenia in which mood is blunted or disjointed, mood disorders show high levels of emotion. For example, patients with bipolar disorder cycle from high cheerfulness and excitability to low depression.

Mood-based (affective)

Manic depression (bipolar disorder), social anxiety disorder, obsessive compulsive disorder, personality and delusional disorders.

17

Lundbeck Belgium Art Collection

18

What are the signs and symptoms of schizophrenia?

The symptoms of schizophrenia are usually divided into positive and negative groups, as described below.

Figure 6: Hallucinations in schizophrenia

Positive symptomsThe positive symptoms of schizophrenia mainly occur in the active periods of psychosis. They are called positive because they are added effects created by the process of the disorder, and therefore tend to be the most outwardly noticeable symptoms. Hallucinations The most common type of hallucination in schizophrenia is auditory (heard). This often involves the person hearing voices in their head having conversations, arguing or commenting on/criticising their actions. These voices may be regular characters to which the person attributes identities. Other less common types of hallucination (that are more often seen in other types of mental disorder) involve tasting, smelling, feeling or seeing things that are not really there. Recordings of brain activity have shown that, during visual or auditory hallucinations, the brain activity of the patient with schizophrenia appears to be the same as that of a real stimulus. In other words, in terms of their brain activity, the patient is experiencing the hallucination as if they were real sensations/experiences (see Figure 6).MRI/PET image showing areas of visual and auditory brain activity (orange) during hallucination.Image from the Science Photo Library.

Delusions Delusions are basically false or unrealistic beliefs. Some delusions are called secondary, which refers to them being interpretations of illusions of hallucinations. For example, if a patient has auditory hallucinations and is hearing voices or hearing thoughts then a secondary interpretation may be that the voices are coming from a transmitter in the fan, in the television set, or even in the persons head. Furthermore, the patient can make the interpretation that an organisation, the CIA for example, is sending the thoughts or voices. In this way the delusion of being under surveillance by the CIA is created. Delusions can also be primary. These are often unrealistic beliefs that seem to arise from nowhere. For

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Signs & symptoms

example, I am god, or My brain is made of gold. These kinds of primary delusions are seen as bizarre, meaning that they are completely unrealistic. Delusions occur at some stage in more than 90% of patients with schizophrenia.1 Disorganised speech, behaviour and thought Another class of positive symptoms involves changes in the pattern of speech, behaviour, and thought. There is a loosening of association between thought and speech, making speech muddled, with illogical jumps between ideas, and producing a disjointed mix of words. Behaviour is also disorganised, with increased agitation and childlike silliness.

Negative symptomsThis class of symptoms is known as negative, because they represent the absence of a usual trait. Negative symptoms occur with varying duration and severity in the periods between active psychotic phases. Negative symptoms include: emotional blunting (affective flattening) impairment of all expression of emotion, e.g., facial expression, body language, vocal tone poverty of speech (alogia) speech that is brief, rarely initiated, or containing little meaningful content avolition general apathy and lack of drive to perform any actions anhedonia inability to experience pleasure social withdrawal avoidance of the company of others, extending to include avoidance of romantic attachments or sexual interest catatonic behaviour unusual postures, mannerisms and rigidity. Interestingly, catatonia was once a characteristic feature of schizophrenia worldwide, but is now predominantly seen in patients from developing countries.2 This class of symptom also includes negativism, which is a refusal to comply with reasonable requests.

Positive symptoms Sarah a 30 year-old single woman with schizophrenia, living with her parents had been repeatedly admitted to hospital following experiences of delusions and hallucinations. Most recently, she had been found wandering the streets in a distressed state as she believed that her every move was being watched through the walls in her own house. However, she was also hearing voices, and these continued outside the house, criticising her behaviour and encouraging her to harm herself. These types of symptoms had been present intermittently for many years, but were now becoming increasingly frequent and more severe.20

Types of schizophreniaNegative symptoms Christopher was hospitalised one year ago, aged 21, in a state of anxiety, and agitation, with persecutory delusions, and auditory hallucinations. He was discharged after two months of successful treatment with an antipsychotic drug. He has since lived with his parents. He was recently persuaded to visit the doctor by his sister, who was concerned about the apparently severe change in his personality. He has given up his regular job for no logical reason, and has become a virtual recluse, spending most of the day in bed. His appearance is unkempt, and he has obviously not washed or shaved for some time. He had previously been close to his family, but in recent months he has mainly stayed in his room and he has often refused to even speak with his sister or parents. As far as his family can say, he has continued his antipsychotic treatment. Due to the large variety of symptoms seen in different patients with schizophrenia, sometimes the disorder is divided into distinct subtypes according to the symptoms that predominate. The three most commonly described subtypes are: paranoid schizophrenia mainly involving thoughts of persecution and being plotted against. Occurs more frequently in men than in women disorganised (hebephrenic) schizophrenia consisting of inappropriate/disturbed emotions, and a profound deterioration of personality. This type of schizophrenia has an early onset catatonic schizophrenia involving extreme withdrawal, lack of speech, and abnormal body positions that can remain fixed for long periods of time.3 The state is sometimes described as a waking coma.

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Cognitive impairmentCognitive impairment can be considered to be a separate condition from schizophrenia, or is sometimes classed as a third category of symptom, alongside the positive and negative signs. Cognition refers to the thought processes that allow functions such as learning, memory, attention, speed of thought, problem solving, planning, and situation assessment. Cognitive impairment reduces the ability to use logical thought, and markedly diminishes quality of life. Cognitive problems are common in patients with schizophrenia, with one study showing that 85% of patients who were almost fully recovered from schizophrenia, still experienced cognitive difficulties.4 Patients with schizophrenia tend to perform badly on a variety of different intellectual tests. Whilst routine, well-learned tasks such as reading and mental arithmetic are often unimpaired, other cognitive tasks, especially those which require a flexible approach to problem solving, are often severely impaired. There is general agreement that patients with schizophrenia exhibit impairment in three main cognitive areas memory, attention, and executive function.5

Assessing symptoms in schizophreniaIn addition to the classification systems used in diagnosis, clinical scales may be used by physicians to follow the progress of a patients symptoms over time. These include the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and the Calgary Depression Scale (CDS).6,7,8

References1. Hirsch SR, Weinberger DR. Schizophrenia. Second edition. Blackwell Publishing, 2005. 2. Concise Medical Dictionary. Sixth edition. Oxford University Press, 2003. 3. Kandel ER, Schwartz JH, Jessell TM. Principles of neural science. Fourth edition. McGraw Hill, 2000. 4. ABPI. Target schizophrenia. May, 2003. 5. Frith C, Johnstone E. Schizophrenia. A very short introduction. First edition. Oxford University Press, 2003. 6. Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychological Reports 1962; 10: 799812. 7. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13 (2): 261276. 8. Addington D, Addington J, Maticka-Tyndale E. Specificity of the Calgary Depression Scale for schizophrenics. Schizophr Res 1994; 11 (3): 239244.

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How is schizophrenia treated?

Currently, there is no cure for schizophrenia, but there are many treatments available to help control symptoms of the disorder and to prevent relapse into psychotic episodes. This control is extremely valuable, and can help a person with schizophrenia to restore elements of normal life. Treatment usually consists of a combination of medication and psychosocial therapy, with a period in hospital often necessary for care and monitoring during psychotic episodes. Treatment for schizophrenia is long-term over a period of years, and appears to be most effective when started early in the course of the disorder.1 However, despite the treatable nature of the disorder, approximately one third of patients are not improved following standard treatment.2

Drug treatment for schizophrenia predominantly involves the use of antipsychotic medications, which help to restore the balance of neurotransmitters in the brain. Antipsychotic medication for schizophrenia was first used in the 1950s, and was shown to be effective in controlling the positive symptoms of the disorder (hallucinations, delusions, etc.). Research has since shown that these typical antipsychotic drugs block the action of the neurotransmitter, dopamine, in the brain (see Figure 7). Figure 7: Dopamine in neurotransmission

Dopamine terminal Dopamine Dopamine (D2) receptor

Chlorpromazine (typical antipsychotic) blocks dopamine binding to dopamine (D2) receptor, preventing signal transmission

23

Treatment

Drug therapy

Newer antipsychotics block both dopamine and serotonin pathways, although the additional effects on the serotonin pathway are, as yet, not so well understood. The serotonin block is believed to contribute to the lower levels of extrapyramidal symptom (EPS) side effects. Increased dopamine in the meso-cortical pathway is thought to be the main reason for positive symptoms. Amphetamines, which stimulate the dopamine pathway, cause similar symptoms which may be indistinguishable from schizophrenia.2 However, the action of antipsychotics to block this pathway can lead to EPS (see Side effects with antipsychotic treatment). In recent years, new atypical antipsychotics have been developed. These are at least as effective on the positive symptoms of schizophrenia as the typical antipsychotics, as well as indicating a possibility of being more effective on the negative symptoms. Atypical antipsychotics also work by altering neurotransmitter (dopamine, serotonin) function in the brain. Their mechanisms of action tend to be different from the typical agents, and this may be related to the atypical antipsychotics tendency to cause fewer severe EPS side effects (see opposite), although they are not free of side effects in general. Drug selection must, therefore, not only take into account the symptoms and needs of the patient, but also balance the riskbenefit in terms of effectiveness and side effects.

Table 2: Examples of antipsychotic drugs*Typical (conventional) antipsychotics Largactil/Thorazine (chlorpromazine) Modecate/Moditen (fluphenazine) Depixol (flupentixol) Haldol (haloperidol) Loxapac/Loxitane (loxapine) Fentazin (perphenazine) Navane (thiothixene) Mellaril (thioridazine) Atypical (new) antipsychotics Solian (amisulpride) Abilify (aripiprazole) Clozaril (clozapine) Zyprexa (olanzapine) Seroquel (quetiapine) Risperdal (risperidone) Serdolect (sertindole) Geodon/Zeldox (ziprasidone)

*Antipsychotic drugs are marketed under a variety of brand names the names given in brackets are the generic (non-proprietary) names. Some may also be known under other proprietary names.

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Side effects with antipsychotic treatment Side effects occur when the antipsychotic drug influences systems other than those involved in schizophrenia. The occurrence of side effects varies from drug to drug, as well as between the general drug classes. A description of some side effects associated with antipsychotic drug use is given in the table opposite.

Table 3: Side effects of antipsychotic drugsSide effect Extrapyramidal symptoms (EPS) Description Set of movement-related side effects (e.g., tremor, stiffness, cramps, involuntary movements, restlessness), that are caused primarily by typical antipsychotic drugs influencing pathways in the brain that control movement, in addition to the psychosis-related pathways. Long-term use of antipsychotic drugs can produce an often irreversible side effect called tardive dyskinesia, which involves uncontrollable muscle movements, usually of the face. Anticholinergic effects, e.g., dry mouth, blurred vision, constipation, dizziness Sedation Seizures Effects caused by the antipsychotic acting non-specifically, and blocking the action of the neurotransmitter, acetylcholine. Common effect of many antipsychotics. Antipsychotic drugs can lower the threshold for seizures. Patients with a history of seizures may have an increased risk. Common effect of many antipsychotics. Elevated levels of the hormone, prolactin, may promote milk production, suppress ovulation, and reduce sexual drive in women. In men, higher prolactin levels can lower sexual drive and may induce impotence. Very rare, but potentially fatal effect that produces problems with breathing and heart rate.

Weight gain Raised prolactin levels

Neuroleptic malignant syndrome (NMS)

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The most common side effects of antipsychotic drugs are EPS side effects: caused by the effect of the antipsychotic on the part of the brain that helps to control movement. There are three basic types of EPS effect: dystonia, akasthisia, and pseudo-parkinsonism. These effects may occur in up to 4060% of patients.2 Other less common side effects include sedation, weight gain, and raised prolactin levels (leading to disruption of sexual function) (see Table 3), although not all of the side effects listed here occur with every drug. There is evidence that some antipsychotics may impair cognitive function, and this has potentially confused the classification of this type of schizophrenia symptom.

Shortcomings of antipsychotic treatmentsRecent evidence suggests that the majority of patients with schizophrenia (74%) will discontinue their medication before 18 months of treatment.3 Patients stop taking their medication for a number of reasons, including inefficacy and intolerable side effects. Each patient has a different profile of symptoms, and each antipsychotic a different profile of side effects, thus it might be expected that there is no simple answer to drug therapy. A good relationship between clinician and patient will prevent the patient from ceasing medication before an alternative can be offered, and switching medication is common before the best balance between symptoms control and side effects is met.

Side effects of drug treatment At age 28, Charlotte had been diagnosed with schizophrenia. Now, aged 50, she has received drug treatment for many years, which has provided reasonable control of symptoms. However, lapses in taking her medication have led to regular admissions to hospital. The reason for her risking stopping the treatment was a feeling of emotional numbness, like being constantly blue. This is a side effect of her medication, interpreted as a very painful mental component of the EPS-syndrome. This has caused social withdrawal and severe lack of motivation, which has often been seen as depression. Her doctor has tried to reduce the dose of her medication to avoid this effect, but this increased her schizophrenia symptoms, leading to the return of disturbing hallucinations.

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Psychosocial and cognitive/ behavioural therapiesPsychological, including behavioural therapies, form a key part of schizophrenia treatment and rehabilitation. These therapies cannot generally help in dealing with acute psychotic phases of illness, but have been shown to reduce the rate of relapse.4 Used in combination with medication, they can help a person with schizophrenia to rebuild their social, functional, and communication skills. Psychosocial support and psychoeducation can be very helpful for the families of people with schizophrenia. Psychotherapy involves regular meetings between the patient and a therapist to talk about their problems and concerns in general, which may or may not be related directly to the schizophrenia. The types of psychotherapy differ, and range from dealing with specific dayto-day problems, to the recall of previous events to guide the patient to insights in their life.2 Behavioural therapy seeks exclusively to change the behaviour of the patient, with the primary aim of addressing the patients ability to deal with social situations.2 Cognitive behavioural psychotherapy focuses on helping the patient to find ways of changing core beliefs and/or thought patterns that cause discomfort, anxiety, depression, or in some way interfere with their life situation.

The supportive nature of these therapies can also encourage patients to comply with their drug treatment a significant concern in this patient population, where approximately 50% of patients fail to take their medication once discharged from hospital.2

Future therapiesDespite innumerable advances in drug treatments over recent decades, there are still many unmet needs in schizophrenia therapy. Obvious improvements would be treatments with increased effectiveness against all types of symptoms, fewer side effects, and rapid action. In addition, treatments are required for patients with symptoms that do not respond to existing therapies (i.e., are refractory). Earlier diagnosis would also be helpful, along with therapies that offered positive effects on conditions that frequently occur alongside schizophrenia such as those involving cognition and mood (see next section What are the co-morbidities of schizophrenia?). Research is ongoing in all of these areas, looking at new approaches to treatment, and maintaining the ultimate aims of discovering a cause and a cure. In the meantime, education to raise awareness and decrease stigma are other valuable ways to improve the lives of those with schizophrenia.

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References1. National Alliance for Research on Schizophrenia and Depression (NARSAD). Understanding schizophrenia. NARSAD, 2003. Accessed online, March 2006. 2. Tsuang MT, Faraone SV. Schizophrenia, the facts. Second edition. Oxford University Press, 1997. 3. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. NEJM 2005; 353 (12): 12091223. 4. Tarrier N. Cognitive behaviour therapy for schizophrenia a review of development, evidence and implementation. Psychother Psychosom 2005; 74 (3): 136144.

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What are the co-morbidities of schizophrenia?

In addition to the symptoms of schizophrenia, some patients will experience co-morbidity that is, additional illness alongside their schizophrenia. The most frequent conditions associated with schizophrenia are mood disorders, such as depression and anxiety. The co-morbidity of substance abuse among individuals with schizophrenia is also high, and around 5070% abuse one or more substances.1 People with schizophrenia and manic depression (bipolar disorder) have higher risks of certain physical conditions than average:2 24 times the rate of cardiovascular diseases 24 times the rate of respiratory disease 5 times the rate of diabetes 8 times the rate of Hepatitis C 15 times the rate of HIV.

Co-morbidity with depression During his teenage years, Michael had experienced mood disorders, and had a problem with obesity. Early in his twenties, he had also been diagnosed with schizophrenia, mainly characterised by the negative signs of isolation and avolition. At this time, Michael received treatment for schizophrenia, along with an antidepressant. Unfortunately, while addressing certain of his symptoms, this therapy increased his weight further, potentiating some of his original problems and impacting upon his health and quality of life.

Mood disordersMood disorders such as anxiety and depression show a high co-morbidity with schizophrenia. Approximately 75% of patients with schizophrenia will experience depression during their lifetime, and this is thought to contribute to an increased risk of suicide.3

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Co-morbidities

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References1. Kosten T, Ziedonis D. Substance abuse and schizophrenia: editors introduction. Schizophrenia Bulletin 1997; 23: 181185. 2. www.rethink.org 3. ABPI. Target schizophrenia. May, 2003.30

What is the social and economic impact of schizophrenia?

Social and economic effects form an important part of living with, and treating, schizophrenia. Schizophrenia is often a difficult disorder for society to accept and deal with, as it influences behaviour, emotion, communication and functional capacity. To live with these symptoms, a person with schizophrenia requires attentive care, which understandably entails extensive costs both personal and financial.

poor articulation, and withdrawal, do not often fit in with a work environment. Further to this, the stress of having to attend work, as well as any stress associated with the work itself, can make symptoms worse. For these reasons, schizophrenia frequently generates a barrier to employment. Education It is under some debate whether patients with schizophrenia suffer a decline in IQ as a consequence of their disorder since, in most cases, an IQ test for the patient prior to diagnosis is not available for comparison. However, a lower IQ is known to be associated with a poorer prognosis.1 Homelessness Approximately 40% of homeless people are thought to suffer from mental illnesses, including schizophrenia.1 Homelessness can be a result of many factors affecting people with schizophrenia, including difficulty fitting into a shared home, broken relationships, loss of employment, desire for isolation, paranoid thoughts and delusions, and a lack of financial support. Drugs, alcohol and violence Abuse of drugs and/or alcohol can be a consequence of the withdrawal from society, loss of employment and homelessness that may affect a person with schizophrenia.31

Social factorsSocial interaction A person with schizophrenia often finds it difficult to integrate socially. This may be because of fear, anxiety or distressing beliefs, or because of symptoms such as poverty of speech and withdrawal, which are not conducive with social activity. In addition, many positive symptoms can be worsened by being exposed to arguments, emotional discussions or large crowds. Poor communication can be a particular hindrance when trying to converse with a physician, making it more difficult for patients to express their needs, and for physicians to assess the disorder severity. Employment The severity and intermittent nature of positive symptoms can make employment practically difficult for a person with schizophrenia. In addition, negative symptoms such as apathy,

Social & economic impact

Estimates indicate that up to 50% of people with schizophrenia are periodic drug or alcohol abusers. Further consequences of this abuse may be an increased likelihood of violence, accidents, financial poverty, and deterioration in appearance. However, patients with schizophrenia are not inherently violent, with anxiety or the side effects of medication often misread as aggression. Suicide and mortality Suicidal behaviour is a common complication of schizophrenia. Some 50% of individuals with schizophrenia will attempt suicide at some time, and it is the cause of death for 613% of patients.2 Along with natural causes, predominantly affecting the heart/blood system, this distressing statistic contributes to the 2.4-fold raised mortality risk in people with schizophrenia.

Social impact At age 24, Carola felt the significant social impact of her recent diagnosis with schizophrenia. She was finding it increasingly difficult to hide her symptoms (changes in behaviour, hallucinations) from her work colleagues in the office where she was employed. The symptoms occurred intermittently, and it was almost impossible for her to predict when her behaviour would change. She was unwilling to speak to her employer about her situation in case she lost her job. Outside work, she felt similarly isolated and less inclined to socialise. Although her friends had noticed some changes in her, she didnt want to tell them about her diagnosis, because of the stigma that is associated with the condition, and the potential change in attitude towards her that this might bring about.

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Economic factorsThe estimated cost of treating a person with schizophrenia for a year is over 100,000. Overall, this is likely to account for approximately 2% of total hospital costs. This includes both pharmacological and nonpharmacological costs. Only 1% of this total cost of care per patient is attributable to the cost of medications, and demonstrates the huge level of non-pharmacological support required by patients with schizophrenia. Although individuals with schizophrenia usually require a period of hospitalisation during their psychotic episodes, there is a rising trend to treat more patients outside the hospital environment a trend that is driven by the increased effectiveness of antipsychotic drugs, as well as changing political priorities. Consequently, the number of hospital beds allocated to patients with schizophrenia in Western Europe has fallen by 3050% over the past 10 years. In addition to direct expenses of care, economic evaluation also takes into account the indirect cost of lost productivity for both the person with schizophrenia, and any friend or family member who has had to limit work in order to act as a carer. These factors all contribute to a considerable association of schizophrenia with poverty. References1. Tsuang MT, Faraone SV. Schizophrenia, the facts. Second edition. Oxford University Press, 1997. 2. ABPI. Target schizophrenia. May, 2003.

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Further information sources Index

This section includes a selection of websites and books that provide further information about schizophrenia.

Websites General information on schizophreniaEUFAMI www.eufami.org EUFAMI is a European network of family and carer associations with the mission to achieve a continuous improvement throughout Europe in mental health, and in the quality of care and welfare, for people affected by mental illnesses; to campaign continuously for the rights of families and carers of people with mental illnesses across the whole of Europe; and to support and strengthen member organisations 48 national and regional voluntary associations in 27 countries in their fight for better health care for those affected by mental illnesses. National Institute of Mental Health (NIMH) www.nimh.nih.gov The National Institute of Mental Health (NIMH) is one of 27 components of the National Institutes of Health (NIH) the United States Federal governments principal biomedical and behavioural research agency. NIH is part of the US Department of Health and Human Services.

The NIMH mission is to reduce the burden of mental illness and behavioural disorders through research on mind, brain, and behaviour. NIMH funds research by scientists across the US as well as in NIMH studies in the internal research programme. Through its extramural programme, NIMH supports more than 2,000 research grants and contracts at universities and other institutions across the country and overseas. Schizophrenia.com www.schizophrenia.com Schizophrenia.com is a US-based non-profitmaking web community that provides information, support and education to the family members, caregivers and individuals whose lives have been affected by schizophrenia. The site contains articles on all aspects of life with schizophrenia, as well as related news items. The site also has discussion and chat boards on various topics, as well as national discussion groups from across the world. Rethink www.rethink.org Rethink is the largest severe mental illness charity in the UK, and aims to improve the lives of all those affected by severe mental illness, whether as a patient, carer, or healthcare worker/professional. Rethink provides a range of community services including employment projects, supported housing, day services, helplines, residential care, and respite centres.

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Further information

National Alliance for Research on Schizophrenia and Depression (NARSAD) www.narsad.org NARSAD is a charity organisation that raises funds for scientific research into the causes, cures, treatments and prevention of severe psychiatric brain disorders, such as schizophrenia and depression. The site contains a brochure on schizophrenia, as well as advice and case stories from people suffering with the illness. Lundbeck Institute www.cnsforum.com The Lundbeck Institute aims to improve the quality of life of people affected by central nervous system disorders, through education. The site contains a section on schizophrenia and a brain explorer animation, which is a visual aid describing disorders of the brain. Schizophrenia Treatment and Evaluation Programme (STEP) www.ncartsforhealth.org/STEP.htm The STEP art gallery displays artwork and poetry by inpatients and clinic outpatients from the University of North Carolina STEP programme. They hope to decrease the stigma associated with mental illness and demonstrate that people with serious mental illnesses (particularly schizophrenia and bipolar disorder) can be creative and productive.

Corporate informationH. Lundbeck A/S www.lundbeck.com This comprehensive site gives a complete overview of Lundbeck, including company history, vision, mission, and product pipeline. Corporate information such as share prices, sales figures and other financial tools are also available.

BooksBirchwood M, Jackson C. Schizophrenia. Psychology Press, 2001. Frith C, Johnstone E. Schizophrenia. A very short introduction. Oxford University Press, 2003. Hirsch SR, Weinberger DR (eds). Schizophrenia. Second edition. Blackwell Science (UK), 2003. McKenna PJ. Schizophrenia and related syndromes. Taylor Francis Group, 1997. Schiller L, Bennett A. The quiet room: journey out of the torment of madness. Little, Brown and Company, 1996. Tsuang MT, Faraone SV. Schizophrenia, the facts. Second edition. Oxford University Press, 1997. Williamson P. Mind, brain, and schizophrenia. Oxford University Press, 2005.

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Abbreviations and glossary

ABPI APA BPRS CDS CIA CSF DSM-IV EPS EUFAMI

Association of the British Pharmaceutical Industry American Psychiatric Association Brief Psychiatric Rating Scale Calgary Depression Scale Central Intelligence Agency (US agency) cerebrospinal fluid Diagnostic and Statistical Manual, 4th edition extrapyramidal symptoms European Federation of Associations of Families of people with Mental Illness Human Immunodeficiency Virus International Classification of Diseases, 10th edition intelligence quotient magnetic resonance imaging

Amygdala A roughly almond-shaped mass of grey matter deep in each cerebral hemisphere. The amygdala have extensive connections with the olfactory system, and also the hypothalamus. The functions of the amygdala are apparently concerned with mood, feeling, instinct, and possibly memory for recent events. Anhedonia A negative symptom of schizophrenia which manifests as an inability to experience pleasure. Avolition A general lack of drive to perform activity of any kind, including those which might constitute daily living. Brief Psychiatric Rating Scale (BPRS) BPRS is a 16-item scale with nine general symptom items, five positive-symptom items, and two negative-symptom items. Completed by the physician, each item is scored on a seven-point severity scale (the higher the number, the more severe the symptom), resulting in a range of possible scores from 16 to 112. For example, the average patient with schizophrenia entering a clinical trial might typically score 33. Catatonic behaviour A negative symptom of schizophrenia involving unusual postures, mannerisms or rigidity.37

HIV ICD-10 IQ MRI

NARSAD National Alliance for Research on Schizophrenia and Depression NHS NIH NIMH NMS PANSS PET STEP WHO National Health Service (of the United Kingdom) National Institutes of Health (US medical agency) National Institutes of Mental Health (US) neuroleptic malignant syndrome Positive and Negative Syndrome Scale positron emission tomography Schizophrenia Treatment and Evaluation Programme World Health Organization

Abbreviations & glossary

Co-morbidity A term used to refer to a disease or disorder that is not directly caused by another disorder but occurs at the same time. Delusion False or unrealistic belief. Dopamine One of many chemicals (neurotransmitters) that send messages between nerve cells. Dystonia A dysfunction of the muscles, characterised by spasms or abnormal muscle contraction. Extrapyramidal symptoms (EPS) A set of movement-related side effects common with antipsychotics, e.g., tremor, stiffness, cramps, involuntary movements, and restlessness. Hallucination Symptom that can be produced by a disease or medications, which makes a person believe they are seeing, hearing, or feeling things that are not really there. Hippocampus An area of the floor of the lateral ventricle of the brain. It contains complex foldings of cortical tissue and is involved in the limbic system.38

Hypothalamus A region of the forebrain, linked with the thalamus and pituitary gland. It contains centres controlling body temperature, thirst, hunger, water balance, and sexual function. It is also closely connected with emotional activity. Limbic system A complex system of nerve pathways and networks in the brain that is involved in the expression of instinct and mood. It includes the activities of the amygdala, hippocampus and hypothalamus. MRI scan Magnetic resonance imaging (MRI) is a type of scan that uses radio waves to generate an image of body tissues. It is especially useful for examining the nervous system, muscles, and bones. Negative symptoms Symptoms which represent the absence of some usual trait, such as blunted emotions, apathy, or social withdrawal. Neuroleptic malignant syndrome (NMS) A very rare, but potentially fatal side effect of some antipsychotics.

Neurological Describing any condition or symptom that affects the nervous system. Neurotransmitter Type of chemical that is present in the nervous system to carry messages between different nerve cells. Examples of neurotransmitters include dopamine, acetylcholine, and noradrenaline. PET scan Positron emission tomography (PET) is a type of scan that can detect chemicals in the brain. It is sometimes used to produce pictures (scans) showing the arrangement of dopamineproducing nerve cells. Positive and Negative Syndrome Scale (PANSS) PANSS is a 30-item scale with 16 general psychopathology symptom items, 7 positivesymptom items, and 7 negative-symptom items. Completed by a physician, each item is scored on a 7-point severity scale, resulting in a range of possible scores from 30 to 210. The positive- and negative-symptom item groups are often reported separately, with a possible range of 7 to 49. For example, a patient with schizophrenia entering a clinical trial might typically score 91.

Positive symptoms Symptoms considered to be added effects of the disorder, such as hallucinations, delusions, and disorganised speech. Prolactin A hormone that stimulates milk production after childbirth and also stimulates production of the male hormone progesterone. Excessive secretion of prolactin can give rise to abnormal production of milk in both sexes. Substantia nigra Area of the brain where dopamine is produced.

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Index

Abilify (aripiprazole) 24 Active period 19 Acute 4, 5, 27 Age of onset 6, 7, 9 Alcohol abuse 8, 14, 31, 32 Alogia 20 American Psychiatric Association (APA) 15 Amisulpride 24 Amygdala 11, 12, 37, 38 Anhedonia 20, 37 Antidepressant 29 Antipsychotic drugs 21, 23 - atypical 24 - discontinuation 26, 27 - side effects 24, 25, 26 - switching 26 - typical 23 Anxiety 5, 8, 21, 29 Apathy 3, 20, 31, 38 Aripiprazole 24 Avolition 20, 29, 37 Bipolar disorder 17, 29 Bleuler, Eugen 3 Blunted emotions 3, 5, 20 Brain tumour 15, 17 Brief Psychiatric Rating Scale (BPRS) 22, 37 Calgary Depression Scale (CDS) 22 Catatonic 20, 21, 37 Cause(s) 1114 - genetic 11, 13 - environmental 11, 14

Chloropromazine 24 Chronic 4, 9 Clinical scales 22 Clozapine 24 Clozaril (clozapine) 24 Cognitive impairment 3, 22, 26 Cognitive symptoms 4, 5, 22 Co-morbidities 5, 27, 29 - cardiovascular disease 29 - respiratory disease 29 - diabetes 29 - hepatitis C 29 - HIV 29 Core symptoms 15 Course 4, 5 Definitions 3739 Delusions 3, 5, 15, 17, 1920, 21, 23, 38 Dementia praecox 3 Depixal (flupentixol) 24 Depression 17, 26, 27, 29 Development 4, 5, 6, 13 Diagnosis 9, 15 Disease course 4 Disease development 4, 5, 6, 13 Disorganised (hebephrenic) schizophrenia 21 Dopamine 11, 23, 24, 38 Drug abuse 8, 14, 15, 29, 31, 32 DSM-IV 15 Dystonia 38 Economic factors 8, 32, 33 - hospitalisation 33

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Index

Epilepsy 15, 17 European Federation of Associations of Families of People with Mental Illness (EUFAMI) 35 Exclusion criteria 15 Extrapyramidal symptom side (EPS) effects 24, 25, 38 - dystonia 26 - akasthisia 26 - pseudo-parkinsonism 26 Fentazin (perphenazine) 24 Flupentixol 24 Fluphenazine 24 Frequency 3, 9 Gender 6, 7, 9, 14 Genetic 11, 13 Geodon (ziprasidone) 24 H. Lundbeck A/S 36 Haldol (haloperidol) 24 Hallucinations 3, 5, 11, 15, 19, 21, 23, 38 Haloperidol 24 Hebephrenic see Disorganised (hebephrenic) schizophrenia 21 Hippocampus 11, 12, 38 Hypothalamus 38 ICD-10 15 Imaging 11, 17 Incidence 7, 9 Kraepelin, Emil 3 Largactil (chlorpromazine) 24 Loxapac (loxapine) 24 Loxapine 24 Loxitane (loxapine) 24 Lundbeck Institute 36

Magnetic resonance imaging (MRI) 19, 38 Maintenance phase 5 Medication 23 Mellaril (thioridazine) 24 Meso-cortical pathway 24 Modecate (fluphenazine) 24 Moditen (fluphenazine) 24 Mood disorder 15, 29 Mortality 5, 32 MRI See Magnetic resonance imaging National Alliance for Research on Schizophrenia and Depression (NARSAD) 36 National Institute of Mental Health (NIMH) 35 National Institutes of Health (NIH) 35 Navane (thiothixene) 24 Negative symptoms 4, 5, 11, 19, 20, 24, 38 Neuroleptic malignant syndrome (NMS) 25, 38 Neurotransmitters 3, 11, 23, 24, 39 Obsessivecompulsive disorder 17 Olanzapine 24 Paranoid 21, 31 Perphenazine 24 Personality disorder 17 PET See Positron Emission Tomography Positive and Negative Syndrome Scale (PANSS) 22, 39 Positive symptoms 5, 1920, 23, 24, 39 Positron Emission Tomography (PET) 11, 19, 39 Prevalence 9 - geographical 9 Prodomal phase 5 Psychiatrist 3, 5, 15 Psychosocial therapy 23, 27

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Psychotic episode 3, 4, 5, 8, 23, 33 Quality of life 8, 29 Quetiapine 24 Relative risk 7 Remission 5 Risperidol (risperidone) 24 Risperidone 24 Schizoaffective disorder 16 schizophrenia.com 35 Schizophrenia Treatment and Evaluation Programme (STEP) 36 Self-care 3, 5, 15, 21 Serdolect (sertindole) 24 Seroquel (quetiapine) 24 Serotonin 24 Sertindole 24 Side effects 24, 25, 26 - anticholinergic effects 25 - extrapyramidal symptoms (EPS) 24, 25, 38 - sedation 25 - seizures 25 - weight gain 25, 29 - prolactin 25, 26, 39 - neuroleptic malignant syndrome 25, 38 - sexual 20, 25, 26, 38 Social anxiety disorder 17 Social factors 8, 31 - social interaction 31 - employment 8, 31 - education 8, 31 - homelessness 8, 31 - drugs, alcohol and violence 3132 - suicide and mortality 32 Social withdrawal 3, 20 Solian (amisulpride) 24

Stigma 3, 8, 27, 32 Suicide 5, 8, 29, 32 Symptoms 3, 4 - core 15 - cognitive 4, 5, 22 - negative 4, 5, 11, 19, 20, 21, 23, 24, 37, 38, 39 - positive 5, 1920, 22, 23, 24, 31, 37, 39 Thioridazine 24 Thiothixene 24 Thorazine (chloropromazine) 24 Treatment 23 See antipsychotic drugs; psychosocial therapy - costs 8, 31, 33 Unmet needs 27 Ventricles 11, 12 Viral infection 14, 17 Winter birth 14 World Health Organization (WHO) 9, 15 Zeldox (ziprasidone) 24 Ziprasidone 24 Zyprexa (olanzapine) 24