ࡱ> @ bjbjFF 4<,, 9 9 98X9d9, |:;;;;;;;^ ` ` ` ` ` ` $[R ?;;?? ;; OOO? ;;^ O?^ OO$rDB ;: .g 9Lz  0 \1OiMOLB OB 8;<O=l=w;;;  48O8Treatment and Management of Schizophrenia (York GP VTS derived from Prodigy, NICE and Medscape) Prognosis About 20% of people who are admitted to hospital for their first episode of schizophrenia do not have another acute episode, and about 25% have no further admissions [Mason et al, 1996]. About 50% of people with schizophrenia treated in standard services will relapse and require re-admission within the first two years of their illness [Mason et al, 1996]. Another 30% of people experience a more continuous illness, where they are never free of symptoms, although the severity of symptoms changes over time. Around 20% of people remain completely resistant to drug treatment, including Clozapine. Factors associated with a poor prognosis Early or insidious onset of schizophrenia Male gender Negative symptoms Family history of schizophrenia Alcohol or drug misuse Low IQ, low social class, or social isolation Significant past psychiatric history Most people experience active psychotic symptoms for 1-2 years before obtaining treatment. Longer periods of untreated symptoms are associated with a lower likelihood of remission, so early identification and referral is important. [Stefan et al, 2002; Barnes and Pant, 2002; Rethink, 2003a] Management Issues  HYPERLINK "http://www.prodigy.nhs.uk/" \l "Role_of_the_GP" Role of the Primary Health Care Team  HYPERLINK "http://www.prodigy.nhs.uk/" \l "Specialist_mental_health_services" Specialist mental health services  HYPERLINK "http://www.prodigy.nhs.uk/" \l "Managing_the_different_stages" Managing the different stages of schizophrenia  HYPERLINK "http://www.prodigy.nhs.uk/" \l "Treatments_used_by_specialist_services" Treatments used by specialist mental health services  HYPERLINK "http://www.prodigy.nhs.uk/" \l "Prescribing_points" Medicines management Role of the Primary Health Care Team Early identification and rapid referral of people experiencing an acute episode of schizophrenia. For most people, the level of distress, anxiety, and subjective confusion they experience, especially during first episodes, leads to difficulty in accessing services [NICE, 2002b]. Monitoring the physical health of people with schizophrenia. Monitoring the adverse effects of antipsychotic drugs. Monitoring the mental health of people with schizophrenia so that they are rapidly re-referred to mental health services if they experience further acute episodes. Around 25% of people with schizophrenia receive all or most of their psychiatric care from their GP [Kendrick et al, 2003]. Therefore, many interventions discussed in this guidance as being the responsibility of specialist mental health services will be the responsibility of the GP. Working in partnership with people with schizophrenia Take time to build a supportive and empathic relationship with the people themselves and their carers. This should be regarded as an essential element of the routine care offered [NICE, 2002b]. Avoid using clinical language. Schizophrenia may affect a person's ability to make judgements, to recognize that they are ill, to comprehend clearly what professionals might say to them, and to make informed decisions about their treatment and care. It is important to give adequate time for discussion and to provide written information, so that the person can give meaningful and properly informed consent before treatment is initiated. Working in partnership with carers The families of people with schizophrenia often play an essential part in the treatment and care of their relative, and with the right support and help can positively contribute to promoting recovery [NICE, 2002b]. Good-quality information about schizophrenia and its treatment should be available to the people themselves and their families. Carers should be provided with information about local family or carer support programmes. These are often run by local branches of charities such as Mind ( HYPERLINK "http://www.mind.org/" www.mind.org), and Re-think ( HYPERLINK "http://www.rethink.org/" www.rethink.org). Some local specialist mental health services may also have carer support groups. However, not all areas have carer support programmes yet. Carers should also have their needs assessed [DH, 1999]. This is often arranged by specialist mental health services, as they are best placed to provide support, and a carer may not necessarily have the same GP as the person with schizophrenia does. However, all carers are entitled to an assessment by social services, irrespective of whether the person is being treated by specialist mental health services or by their GP. Specialist mental health services Co-ordinated care is delivered using the care programme approach (CPA). The CPA is a holistic approach that aims to assess, treat, and support people with schizophrenia in the community, rather than during an in-patient stay. It is based on four principles [DH, 2002a]: Assessment (including an assessment of risk to self and others). Allocation of a care co-ordinator (or 'key worker'). Development of a care plan. This should include all the arrangements for follow-up, responsibility for physical health checks, and the arrangements for social group activities and physical activities. It may also include advance directives covering the action to be taken in the event of specific circumstances (e.g. relapse). Review. Multidisciplinary teams deliver this care (e.g. community mental health teams, early intervention teams, assertive outreach teams, and crisis resolution/home treatment teams). These teams specialize in more intensive and comprehensive treatment to enable many people who would previously have been treated as in-patients to be treated in the community. However, many people with schizophrenia have complex health and social care needs that cannot all be met by one team. 'Enhanced' CPA is used to co-ordinate care between all the different agencies involved. The care co-ordinator is the main mechanism of managing and integrating an individual's care between all specialist mental health services, social services, and primary care (GPP). The care co-ordinator is often a nurse, but can also be the social worker, or occupational therapist. What do the different mental health teams do? Note: not all of these services are available in every Strategic Health Authority. Community mental health teams (CMHT) provide the core of local specialist mental health services, and offer assessment, treatment, and social care to adults with mental health problems in the community. They operate from a mental health resource centre that is based away from the main hospital site, in order to be easily accessible to clients. In many areas, the CMHT is the gateway to the more specialized teams (such as assertive outreach teams, etc) [DH, 2002b]. People are referred to the CMHT for an initial assessment, and then placed with the team that best suits their needs. Early intervention teams (where they exist) can often be accessed directly by the GP. Some areas have direct access to all their specialist mental health teams, but this is a less widespread strategy for organizing services. In-patient care is the most widely available option for people who need rapid assessment and stabilization during an acute episode. This includes people who need compulsory care under the Mental Health Act because they are so severely ill that they cannot make a decision about treatment, or because they refuse any type of treatment. Crisis resolution/home treatment teams enable people to be treated at home (instead of as in-patients) for an acute episode of schizophrenia. They can also be used to augment the services provided by early intervention services and assertive outreach teams (C) [NICE, 2002b]. They are the only specialist mental health team that is available to help with crises that occur outside normal office hours. Acute day hospital is another alternative to in-patient care, and also facilitates early discharge from in-patient care [NICE, 2002b]. Assertive outreach teams (also known as assertive community treatment): this service delivers intensive treatment and rehabilitation in community settings for the severely mentally ill. They provide rapid help in crises. Staff will visit people at home, act as an advocate, and liaise with other services such as the GP or social services. People using this service often need help to find housing, secure an adequate income, and sustain basic daily living (e.g. shopping, cooking, and washing) [DH, 1999]. The teams are better at keeping in touch than ordinary services are, and are useful for people who have a history of poor engagement with services, leading to frequent relapse and/or social breakdown (B) [NICE, 2002b]. They should provide care for homeless people with schizophrenia. Early intervention teams are not yet available in many areas. They provide early identification and treatment of people aged between 14 and 35 years who have the first symptoms of schizophrenia. Early intervention teams are intended to provide the optimum mix of specialist pharmacological, psychological, social, occupational, and educational interventions at the earliest opportunity [DH, 1999]. Managing the different stages of schizophrenia Acute episode of schizophrenia First episode of schizophrenia Early treatment of schizophrenia is associated with a better prognosis. The GP is likely to be the first point of contact for someone who may be developing schizophrenia for the first time. Anyone with suspected, or newly diagnosed, schizophrenia should be referred urgently to specialist mental health services for assessment and development of a care plan [NICE, 2002b]. Part of the urgent assessment should include an early assessment by a consultant psychiatrist, if there is a presumed diagnosis of schizophrenia [NICE, 2002b]. Sometimes, because of the distress, anxiety, and confusion caused by the illness, the person will refuse all requests by the family to see the GP. If the history given by the family is suggestive of schizophrenia, every effort should be made to assess the person. If the person is unwilling to come to the surgery (generally because of a lack of insight into the illness), then a home visit should be attempted. Depending on the circumstances, the home visit could be by the GP, or by the GP and a consultant psychiatrist. If the person refuses a home visit, but the history suggests schizophrenia, a referral for assessment should be made to the Community Mental Health Team. GPs should have a high level of suspicion for schizophrenia. Schizophrenia is often (but not always) preceded by a long prodromal period with a range of ill-defined, insidious, and non-specific symptoms that result in a gradual deterioration in personal functioning. Many people present to primary care with non-specific symptoms such as peculiar or uncharacteristic behaviour, poor communication, unusual ideation, social withdrawal, poor personal hygiene, or reduced interest and motivation. Most do not go on to develop schizophrenia. Nevertheless, people presenting with these types of symptoms should be monitored in primary care [National Collaborating Centre for Mental Health, 2003]. Of the minority that do develop schizophrenia, some will develop 'attenuated' positive symptoms first, for example mild thought disorders, ideas of reference, suspiciousness, odd beliefs, and perceptual distortion. Attenuated positive symptoms are milder than those seen in established schizophrenia [National Collaborating Centre for Mental Health, 2003]. People with possible attenuated positive symptoms should be referred to specialist mental health services for assessment. Consider starting an atypical antipsychotic if there are acute symptoms of schizophrenia, but the person is unlikely to be assessed by specialist mental health services for a few weeks [NICE, 2002b]. Where possible, treatment should be discussed with specialist mental health services before it is started. Referral to specialist mental health services The action to be taken when crisis occurs should be documented in the care plan of anyone with established schizophrenia [DH, 2002b]. The care co-ordinator should be informed, and will generally liaise with the relevant specialist mental health team to provide rapid assessment and treatment. If this is the first episode of schizophrenia that the person has experienced, or if the action in the event of crisis is not documented in the care plan, contact the community mental health team (CMHT). They will assess the individual, and refer them on to the team that knows the individual best, or that best suits the current need: First episode of schizophrenia: eventually the person will be managed by early intervention services (EIS). However, EIS are not yet available in most areas. Acutely disturbed, at risk, and needs high level of support: managed by the crisis resolution/home treatment team (if this service is available) or by the in-patient unit. Not acutely disturbed and at less risk: managed by the CMHT or assertive outreach team. Specialist community-based teams unavailable, or unable to meet the needs of the person, or compulsory treatment needed under the Mental Health Act: refer to in-patient unit. Acute Day Hospital services are an alternative to acute admission to in-patient services in some areas. Availability of services varies within regions. Specialist teams such as crisis resolution/home treatment teams or early intervention services are not currently available in all strategic health authorities. People who have positive symptoms but are not at high risk should be assessed routinely. Routine assessments should be made within a week if possible, but no longer than 4 weeks after referral [DH, 2002b]. If a crisis occurs out of hours, contact the local crisis resolution team, crisis helpline, duty psychiatrist, or duty social worker. Consider contacting the police if there is a risk of self-harm or injury to others, or if the person is causing a civil disturbance. People at high risk of harm to self or others Someone who is at high risk of self-harm or of harm to others needs urgent assessment, within a maximum of 24 hours. Local arrangements for urgent assessment vary. In some areas, the person would be admitted directly to in-patient services by the GP. In other areas, the community mental health team is the single point of access for all referrals. They notify the appropriate team for the initial assessment (e.g. the crisis resolution/home treatment team or in-patient services). In potentially violent situations, it is important to try to de-escalate the situation. The police have specific training in talking people down, and should be called if there is an imminent risk of harm occurring. GPs should not use rapid tranquillization. Rapid tranquillization is extremely traumatic, and is likely to severely damage the relationship between the individual and the GP. There are also significant medical risks involved, such as loss of consciousness instead of sedation, or over-sedation with loss of alertness. Resuscitation equipment and drugs, including flumazenil, must be available and easily accessible if rapid tranquillization is used. This is very unlikely to be the case in primary care. Tranquillization using oral lorazepam (e.g. 1 mg) is an option, provided that the person is willing to accept oral medication. Use of the Mental Health Act Many people with a serious mental illness will enter specialist mental health services voluntarily for assessment and treatment. The Mental Health Act is used only when detainment in hospital is considered necessary for the health and safety of the person with schizophrenia, or for the protection of others. A GP is most often involved in the use of section 2, which allows someone to be detained in hospital for assessment for up to 28 days. A GP can also be involved in the use of section 3, which allows someone to be detained in hospital for treatment. Sections 2 and 3 require an application to be made based on two medical recommendations - often these are from the consultant psychiatrist and the GP. The GP's opinion is as important as that of the psychiatrist, as the GP will often know the person best, and be familiar with what is 'normal' for that person. Section 4 is rarely used, but allows someone to be detained in hospital for emergency assessment. It is based on the recommendation of only one doctor, often the GP. Section 4 is used only in extremely urgent situations (e.g. emergency admission is needed because of a very high risk of suicide or harm to others). Some GPs (although not many) are 'section 12 approved'. This means that they can provide a psychiatric opinion in their own right. [Andreasen et al, 2000] Early post-acute period Most people will be managed by specialist mental health services during this period. The health and social care needs of people with schizophrenia should be assessed comprehensively (by specialist mental health services). The assessment should cover medical, social, psychological, economic, occupational, physical, and cultural issues (GPP) [NICE, 2002b]. Each person with schizophrenia should have a care plan and a named care co-ordinator (key worker). A copy of the care plan should be sent to the GP. Plans for recovery should include psychological treatments and medication advice (see  HYPERLINK "http://www.prodigy.nhs.uk/" \l "Treatments_used_by_specialist_services" Treatments used by specialist mental health services). The social needs of the individual should be addressed. People may need direct practical help with a range of basic needs, such as obtaining benefits, shopping, help with keeping appointments, etc. Others may benefit from being taught these basic skills. Some people may need advocacy with other agencies (for example landlords and employers) [DH, 2002b]. People should be encouraged to seek work where possible. They may need practical help with filling in application forms or accompaniment to job interviews [DH, 2002b]. Some areas have supported employment programmes that help to place people with schizophrenia in employment [National Collaborating Centre for Mental Health, 2003]. Educational opportunities are also important. They can provide extra skills and provide a structure to the day [DH, 2002b]. Recovery phase Care should be co-ordinated between the different agencies involved (e.g. social workers, specialist mental health team, and GP). Each person with schizophrenia who is referred to specialist mental health services should have a named care co-ordinator responsible for this. The risk of relapse after an acute episode is high. Relapse occurs in around 80% of untreated people with schizophrenia. Antipsychotics are therefore continued for 1-2 years from the start of recovery, as maintenance therapy significantly reduces the relapse rate. People with schizophrenia should have their mental and physical health reviewed regularly [NICE, 2002b]. GPs are best placed to monitor the physical health of people with schizophrenia. Primary care professionals should also monitor the mental health of a person with schizophrenia, so that people can be referred before crises arise, wherever possible. This is particularly important when individuals are no longer being regularly reviewed by specialist mental health services. The frequency of checks should be a joint decision by the person and the clinician. The agreed frequency should be recorded in the person's notes (GPP) [NICE, 2002b]. We suggest that people should have their physical health and mental health reviewed at least annually. Mental health will often need to be reviewed more frequently, depending on the stability of symptoms. Physical health checks should be undertaken at least annually, as people with schizophrenia have a higher risk of coronary heart disease than is found in the general population. Smoking, obesity, and a poor diet are common. Specialist mental health services should undertake regular and full assessment of the mental health of the users of their services. If a person with schizophrenia does not want physical health to be monitored by the GP, specialist mental health services should be informed, and they should take on this role [NICE, 2002b]. Physical health checks for people with schizophrenia Monitor increased risk of cardiovascular disease. People with established cardiovascular disease should receive secondary prevention measures. All other people with schizophrenia should have their 10-year coronary heart disease risk calculated annually (primary prevention). All people with schizophrenia should have their blood pressure (BP) measured regularly (primary prevention), and treated as necessary. People who are found to have high BP should be screened for hyperlipidaemia, and treated as necessary. Consider routine urine/blood-glucose screen for diabetes. Offer advice and encouragement about smoking cessation, a healthy diet, and exercise. Obesity is common, and can be due to a combination of a poor lifestyle and weight gain caused by antipsychotic drugs. A healthy diet and exercise is often the only way to reduce drug-induced weight gain. Advice should be personalized and achievable. Ask about adverse effects of drug treatment. Include extrapyramidal symptoms and tardive dyskinesia. Include common adverse effects such as sexual dysfunction and lethargy. Consider routine weight monitoring, particularly for drugs that are known to cause weight gain (e.g. Olanzapine). Check an electrocardiogram (ECG) if the person is taking a drug or dose with a higher risk of QT prolongation (e.g. Thioridazine, Zotepine, high-dose haloperidol [more than 20 mg per day]) or a dose of any antipsychotic that is above the British National Formulary upper limit. Ask about alcohol or illicit drug use. People with suspected substance-misuse problems should be re-referred to specialist mental health services. [BNF 44, 2002; NICE, 2002b; Taylor, 2003] When should re-referral be considered? The decision to re-refer a person with schizophrenia should take account of the person's view, and, where appropriate, the carer's. Issues of confidentiality should be respected when involving carers. People should be referred back to specialist mental health services if: They are at increased risk of harm to themselves or others (referral should be urgent) They are showing symptoms of relapse (some people have very specific 'relapse signatures', and these should be documented in the care plan) They are not responding well to treatment They are not taking their treatment, or you suspect this You suspect they are misusing alcohol or drugs The features of the episode differ from those of previous episodes They require a second opinion They have just joined the practice (for formal assessment and development of a care plan) The GP feels unable to meet the individual's needs The family or carer is not coping [NICE, 2002b; DH, 2002b; NHS Modernisation Agency, 2003] Driving Driving must stop during any acute psychotic episode, and the Driver and Vehicle Licensing Agency (DVLA) must be notified. The General Medical Council guidelines advise breaking patient confidentiality and informing the DVLA if the person is unable to appreciate that driving during psychosis is unsafe (i.e. because of lack of insight into their illness), or if the person refuses to stop driving. Re-licensing for an ordinary driving licence is considered when the person has remained well and stable for at least 3 months, and is free from adverse effects of medication that impair driving. The person must also be compliant with treatment - drivers with psychiatric illnesses are often safer when well and on regular medication than when they are ill. People who have continuing symptoms, or limited insight, can still be considered for relicensing provided that their symptoms do not make them unfit to drive (e.g. poor concentration, or memory impairment). Antipsychotic drugs can cause sedation, poor concentration, and extrapyramidal symptoms, which can all potentially impair driving. Careful assessment is therefore needed to determine whether adverse effects of medication will impair driving. This is usually undertaken by specialist mental health services. A holder of a licence for heavy goods vehicles or passenger-carrying vehicles will be considered for re-licensing only after remaining well and stable for a minimum of 3 years. People should inform their motor vehicle insurance company of the diagnosis. [DVLA, 2000; NHS direct, 2003] Treatments used by specialist mental health services Psychological interventions Note: not all psychological interventions are currently available in every strategic health authority. Psychological treatments are an essential part of the treatment options for relapse prevention and for symptom reduction. There is most evidence for cognitive behavioural therapy (CBT), and for family interventions (A) [NICE, 2002b]. CBT should be offered to people with schizophrenia who are experiencing persistent psychotic symptoms (A). It should also be considered as a treatment option to assist in the development of insight (B), and to manage poor treatment adherence (C) [NICE, 2002b]. CBT depends upon an effective therapeutic alliance between the clinician and the affected person. CBT encourages people to establish links between their thoughts, feelings, or actions with respect to current or past symptoms, and then re-evaluate their perceptions, beliefs, or reasoning related to the target symptom [National Collaborating Centre for Mental Health, 2003]. Family interventions should be available for families who are living with people with schizophrenia, or who are in close contact with them (A) [NICE, 2002b]. A high level of 'expressed emotion' within a family has been shown to be an effective predictor of relapse in schizophrenia. This might be the case, for example, in families that are excessively critical, hostile, or over-involved towards the person with schizophrenia. These sessions can improve symptoms and reduce the chance of another acute episode. They are also helpful for people who are at risk of a crisis occurring, or who have persisting symptoms. Family intervention sessions generally involve the person with schizophrenia as well as the family. They use psycho-educational interventions, or problem-solving/crisis-management work. This aims to help families cope with their relative's illness more effectively, reduce levels of distress, improve the way the family communicates, and provide support and education for the family [National Collaborating Centre for Mental Health, 2003]. Counselling and supportive psychotherapy are not recommended unless CBT is not available locally. However, the individual's preferences should always be taken into account (C) [NICE, 2002b]. Pharmacological interventions Antipsychotic drugs are used to control acute episodes of schizophrenia, and to prevent relapse. Drugs are also necessary for psychological treatments to be effective. They are only one part of a comprehensive package of care that aims to keep a person stable enough to live as normal a life as possible. Antipsychotics are most effective at controlling positive symptoms (e.g. hallucinations and delusions). They are generally less effective at controlling negative symptoms. The atypical antipsychotics may be slightly more successful at treating secondary negative symptoms, but they have little effect on primary negative symptoms [Stefan et al, 2002]. Low-dose Amisulpride (50-300 mg per day) has been shown to reduce negative symptoms when compared to placebo [BNF 44, 2002]. However, a different study found no difference between low-dose Amisulpride and low-dose Haloperidol in negative symptom improvement. The final choice of antipsychotic should be a joint decision between the clinician and the individual. Atypical antipsychotic drugs should be considered in the choice of first-line treatments for schizophrenia. The final choice will depend on the balance of the benefits of a drug and its adverse effect profile. This should be discussed fully with the individual [NICE, 2002a]. Doses at the lower end of the standard dose range should be used when starting treatment, and the minimum effective dose should be used [NICE, 2002b]. Continuous dosing should be used. Intermittent dosage maintenance strategies should be avoided, because of the increased risk of symptoms worsening or relapse. They should only be considered for people who refuse maintenance treatment, or who have some other contraindication to continuous dosing such as adverse-effect sensitivity (C) [NICE, 2002b]. If a typical antipsychotic is used for an acute episode, the dose should be within the range of 300-1000 mg chlorpromazine equivalent per day for a minimum of 6 weeks [NICE, 2002b]. There is no benefit in using loading doses, rapid dose escalation, or very high maintenance doses [National Collaborating Centre for Mental Health, 2003]. The person should be treated with only one antipsychotic drug at a time, apart from during short periods to cover changeover (C) [NICE, 2002b]. A person who does not improve after 6-8 weeks of a therapeutic dose should be switched to another antipsychotic. Consider using olanzapine or risperidone, if not previously tried. (They have been shown to benefit some people with treatment-resistant schizophrenia, but there is less evidence of improvement than with clozapine [National Collaborating Centre for Mental Health, 2003].) Adjunctive treatments (e.g. lithium, carbamazepine, sodium valproate, and lamotrigine) may also be used by specialist mental health services to augment the action of antipsychotic drugs. Their use was outside the scope of the current National Institute for Clinical Excellence (NICE) guideline, but it is anticipated that they will be reviewed by NICE in the future. If non-adherence is the reason for treatment failure, consider using a depot preparation. If non-adherence is due to intolerable adverse effects, switch to another oral preparation with a different adverse-effect profile. If there is evidence of treatment-resistant schizophrenia, clozapine should be started as soon as possible: a person who does not respond to a second antipsychotic after a further 6-8 weeks of treatment should be switched to clozapine [NICE, 2002a]. Maintenance treatment Antipsychotics are generally continued for 1 to 2 years to prevent further relapses, but this should be discussed with the individual (GPP) [NICE, 2002b]. About 20% of people with schizophrenia will experience only one episode of schizophrenia in their lifetime. A similar percentage will still experience relapse despite maintenance treatment. It is not possible to identify these people, other than over time. Therefore antipsychotic maintenance treatment should be considered for anyone diagnosed with schizophrenia [National Collaborating Centre for Mental Health, 2003]. Withdrawal from antipsychotic medication should be undertaken gradually, whilst regularly monitoring signs and symptoms for evidence of potential relapse (GPP) [NICE, 2002b]. Following withdrawal from antipsychotic medication, people should be monitored regularly for signs and symptoms of potential relapse for at least 2 years, as the rate of relapse following treatment withdrawal is high. Types of antipsychotic drugs The research concerning the relationship between dopamine type 2 (D2) receptor activity and the symptoms of psychosis and treatment response is highly compelling, with convergent evidence indicating that sufficient levels of blockade of D2 transmission is associated with a clinical antipsychotic response, while excessive blockade of D2 transmission can be associated with extrapyramidal symptoms (EPS), such as parkinsonism. This had led to the concept of a therapeutic window for antipsychotic dosing. The typical antipsychotics exert their therapeutic action by blocking dopamine receptors (D2). Typical antipsychotics include Chlorpromazine, Thioridazine, and Trifluoperazine (phenothiazines); Haloperidol (butyrophenone); Flupentixol and Zuclopenthixol (thioxanthenes); and Sulpiride. These are established drugs that have a long safety record, but extrapyramidal effects, hyperprolactinaemia, sedation, and tardive dyskinesia are common. The atypical antipsychotics are structurally diverse, with different adverse-effect profiles. They include Amisulpride, Clozapine, Olanzapine, Quetiapine, Risperidone, and Zotepine. While many atypicals block both serotonin receptors and dopamine receptors, this is not the case with them all (e.g. Amisulpride blocks only dopamine receptors). The term 'atypical' is now broadly used to mean the newer antipsychotics. Atypical antipsychotics are thought to have a lower potential risk of extrapyramidal symptoms than typicals have. Medicines management Who should start treatment for a first episode of schizophrenia? Generally, antipsychotics are started only by specialist mental health services, after an initial assessment. However, if it is the person's first acute episode of schizophrenia but the person is unlikely to be assessed urgently by specialist mental health services, consider starting an atypical antipsychotic if there are acute symptoms of schizophrenia [NICE, 2002b]. For example, a person with florid psychotic symptoms but who is not at imminent risk of self-harm, or of causing harm to others, will often be give a routine appointment. Such a person will usually be seen within a few weeks of referral [DH, 2002b]. Where possible, treatment should be discussed with specialist mental health services before it is started. Discuss the use of antipsychotic drugs with the person, and decide jointly which to use. It is important to give adequate time for discussion, and to provide written information, so that the person with schizophrenia can give meaningful and properly informed consent before treatment is initiated [NICE, 2002b]. If the person is at risk of suicide or there is a risk of violence to others, refer urgently (or as an emergency) to specialist mental health services. Choice of oral atypical antipsychotic for a first episode (if initiation is appropriate in primary care) Note: this section does not include Clozapine as it can be started only by specialist mental health services. Atypical antipsychotics, at the lower end of the dose range, are the preferred treatments for a person experiencing a first episode of schizophrenia. This is because of the presumed lower potential risk of extrapyramidal symptoms [NICE, 2002a]. Cerebrovascular disease: where possible, avoid starting Risperidone and Olanzapine in people with a history of stroke or transient ischaemic attack. Consideration should also be given to other risk factors for stroke such as hypertension, diabetes, current smoking, and atrial fibrillation [CSM, 2004]. Studies are ongoing to confirm whether there is an increased risk of cerebrovascular disease with other atypical antipsychotics. Cardiovascular disease: people with angina or a previous myocardial infarction (MI) should avoid Zotepine, Risperidone, and Quetiapine. These drugs reduce blood pressure, resulting in a reflex tachycardia that may exacerbate angina. (Phenothiazines also have this effect.) Olanzapine may be a safer alternative in someone with angina, or with a previous MI, as it rarely causes hypotension [Taylor et al, 2001]. Cardiovascular disease: arrhythmias. Most antipsychotic drugs have the potential to affect the QT interval. Arrhythmias are more likely to occur in the presence of hypokalaemia, hypocalcaemia, or hypomagnesaemia; or with concomitant administration of other drugs that also prolong the QT interval, or reduce the clearance of antipsychotics. Amisulpride is probably safe in people with arrhythmias. Zotepine (and Sertindole) should not be used. Phenothiazines, higher doses of Haloperidol (more than 20 mg per day), and doses above the British National Formulary upper limit should also be avoided [Taylor, 2003]. Risperidone and Olanzapine should also be avoided in people with atrial fibrillation because of concerns about an increased risk of stroke [CSM, 2004]. Epilepsy: all antipsychotic drugs can lower the seizure threshold. The incidence of seizures was low in clinical trials of Olanzapine, Risperidone, and Quetiapine. Whichever antipsychotic is chosen, it is still prudent to use a low starting dose, and to increase the dose slowly in someone with epilepsy. Additional risk factors for seizures are head injury, previous seizure history, concomitant drugs that reduce the seizure threshold, and withdrawal from central depressants (for example alcohol, benzodiazepines, barbiturates etc). Diabetes: the incidence of type 2 Diabetes is more common in people with schizophrenia than in the general population. Drug treatment with antipsychotics may increase this risk, although a causal relationship has not been firmly established. Both typical and atypical antipsychotic drugs have been associated with an increased risk of diabetes, but the risk seems to be highest with Clozapine and Olanzapine [Sernyak et al, 2002; Lean and Pajonk, 2003]. Angle-closure glaucoma, prostatic hypertrophy, or urinary retention: most atypical antipsychotics cause antimuscarinic adverse effects. Tolerability may be slightly improved with Amisulpride [Stanniland and Taylor, 2000]. Avoid Zotepine and Olanzapine. Non-smokers: Olanzapine is metabolized more slowly by non-smokers, women, and the elderly. Consider a lower starting dose of Olanzapine (5 mg once a day) in people with more than one 'risk factor' for slow metabolism to reduce the risk of adverse effects, for example a female and a non-smoker. Elderly people: elderly people are at higher risk of postural hypotension, extrapyramidal symptoms, and antimuscarinic effects, especially when starting therapy. Start with a lower dose, and titrate slowly [Taylor et al, 2003]. Adverse effects of antipsychotics Antipsychotics cause a wide range of adverse effects including sedation, weight gain, hyperprolactinaemia, and sexual dysfunction, as well as extrapyramidal symptoms (movement disorders) such as Parkinsonism, akathisia (lower-limb restlessness), and dystonia (abnormal movements of the face and body). Tardive dyskinesia (TD) is a late-onset movement disorder that can occur with prolonged use of antipsychotics. It is characterized by rhythmical, involuntary movements; usually lip smacking and tongue rotating, although it can affect the limbs and trunk. It may be irreversible, and can sometimes worsen on treatment withdrawal. Around 20% of people treated with typical antipsychotics eventually experience TD. (The incidence is roughly 5% each year.) The emergence of extrapyramidal symptoms is a strong risk factor for later TD [Casey, 1997]. Older people are at higher risk, even with short-term treatment with antipsychotics [Jeste et al, 1999]. Differences between drugs Typical antipsychotics can potentially cause any of the adverse effects listed above, as well as antimuscarinic symptoms (e.g. dry mouth, blurred vision, urinary retention, constipation, and cutaneous flushing). They can also cause postural hypotension; photosensitivity; reduced seizure threshold; QT prolongation; and occasionally corneal and lens opacities, and purplish pigmentation of the skin, cornea, conjunctiva, and retina. Although they all tend to cause these adverse effects, the intensity varies between the different types of typical antipsychotic drugs [BNF 44, 2002]: Group 1 phenothiazines (Chlorpromazine): pronounced sedative effects but moderate antimuscarinic and extrapyramidal effects. Group 2 phenothiazines (Thioridazine): moderate sedative effects, marked antimuscarinic effects, and fewer extrapyramidal symptoms (EPS) than groups 1 and 3. Group 3 phenothiazines (Fluphenazine, Trifluoperazine): fewer sedative and antimuscarinic effects, but more EPS than groups 1 and 2. Butyrophenones (Haloperidol): similar to group 3 phenothiazines. Flupentixol, Sulpiride, and Zuclopenthixol: similar to group 3 phenothiazines. Atypical antipsychotics have more diverse adverse-effect profiles. They cause fewer extrapyramidal effects than do typical antipsychotics, but their overall tolerability is similar [Geddes et al, 2000]. It is hoped that the lower rate of EPS will translate into a lower rate of tardive dyskinesia (TD). However, there is very little long-term trial data available on comparative rates of TD between atypicals, or between typical and atypical drugs [NICE, 2002a]. In addition, a recent meta-analysis suggested that the rate of EPS might not be significantly different between atypical antipsychotics and chlorpromazine, if chlorpromazine was used at doses of less than 600 mg per day [Leucht et al, 2003]. Weight gain has emerged as a significant and troublesome adverse effect with atypical antipsychotics. The risk of weight gain varies with individual drugs [Taylor et al, 2003]: High risk: Clozapine and Olanzapine Moderate/high risk: Zotepine and Thioridazine Moderate risk: Risperidone, Quetiapine, and Chlorpromazine Low risk: Amisulpride, Haloperidol, and Trifluoperazine Type 2 diabetes has been linked to Clozapine and Olanzapine. QT prolongation has emerged as a problem with Zotepine and Sertindole. Hyperprolactinaemia is less common with most atypical antipsychotics, but it can still be a problem with Risperidone, Amisulpride, and Zotepine. Insomnia, anxiety, and agitation are also common with Amisulpride, Risperidone, and Zotepine. Sedation is common with Clozapine, Olanzapine, Quetiapine, and Zotepine. A three-fold increase in the risk of stroke has been observed in studies of Risperidone and Olanzapine in elderly people with dementia [CSM, 2004]. Although no similar data are available on younger people with schizophrenia, it would seem prudent to avoid starting Risperidone and Olanzapine in any person with a history of stroke or transient ischaemic attack or with risk factors for stroke such as hypertension, diabetes, smoking, and atrial fibrillation. However, if they are already well controlled on Risperidone and Olanzapine the decision is less clear, and specialist advice should be sought before treatment is switched or gradually withdrawn [RCGP, 2004].  HYPERLINK "http://www.prodigy.nhs.uk/" \l "table3" Table 3 highlights the differences in the incidence and intensity of adverse effects between selected antipsychotics. Table 3. Adverse effect profiles of a selection of antipsychotic drugs EPSWeight GainHyper-prolactinaemiaSedationAnti-muscarinic effectsTardive dyskinesiaBlood dyscrasiasChlorpromazine+++++++++++++++++Haloperidol++++++++++++++Clozapine-+++-++++++-+++Olanzapine+/-+++++++?-Quetiapine-++-+++?+Risperidone+++++++-+?-Zotepine+++++++++?+Amisulpride++++++--+?-Key: +++ high; ++ moderate; + low; - very low/zero; ? data not available. EPS = extrapyramidal symptoms Table reproduced from Andreasen et al, 2000Adverse effects rating scales Although tardive dyskinesia is a severe social handicap, about 80% of people remain free from it. Sexual dysfunction, sedation, and weight gain are often the adverse effects that people with schizophrenia find the most distressing [Day et al, 1998] and adverse effects are a common cause of non-compliance with treatment. The Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) can be used to assess the severity of adverse effects, and takes only 5 -20 minutes to complete. No specialist training is needed to use it, and people with schizophrenia can often complete it without supervision [Day et al, 1995]. It is often most practical to obtain a baseline LUNSERS score once psychotic symptoms have settled. A copy of LUNSERS can be found in the PRODIGY patient-information leaflets. Important: before using LUNSERS the authors require that you register your usage at  HYPERLINK "http://www.lunsers.org.uk/" www.lunsers.org.uk. Alternatively write to Symplex Information Solutions Ltd, 25 Bentley Road, Liverpool, L8 0SZ briefly stating the purpose for which you intend to use the scale. A computerised autoscore version of LUNSERS and different language versions of LUNSERS are also available from  HYPERLINK "http://www.lunsers.org.uk/" www.lunsers.org.uk. Switching antipsychotics Switching antipsychotics needs to be done with care, and we recommend that people be referred to specialist mental health services if a switch is needed. Antipsychotics should not be stopped suddenly, as this can precipitate relapse, or cause withdrawal reactions such as cholinergeric rebound (e.g. nausea, restlessness, anxiety, insomnia, etc) or withdrawal dyskinesias (e.g. extrapyramidal symptoms, or rebound akathisia) [Bazire, 2001]. The dose of the original antipsychotic should be tapered down slowly (generally over at least 8 weeks), while the new drug is slowly increased. The dose of any antimuscarinic drugs will also need to be stopped slowly. There is a lack of agreement about equivalent doses of antipsychotic drugs [Bazire, 2001]. The British National Formulary gives approximate equivalent doses of some antipsychotics, but the equivalent doses of several atypical antipsychotics are not yet known. Minimizing common adverse effects Many people with schizophrenia are on the enhanced care programme approach (CPA), and the community mental health team will often deal with the management of adverse effects. However, 25% of people with schizophrenia are still managed mainly by their GP [Kendrick et al, 2003], and minimizing adverse effects is an important aspect of care. (Note: a person who may benefit from switching drugs should be referred to specialist mental health services.) The information below regarding switching drugs is based upon the Maudsley 2001 Prescribing Guidelines [Taylor et al, 2003]. Weight gain is common with all antipsychotics, but may be particularly severe with clozapine and olanzapine. The social stigma associated with being 'fat' adds to the stigma experienced by people with schizophrenia, and is a common reason for non-compliance. Most weight gain seems to occur in the first 6-9 months of treatment and then generally reaches a plateau. Good advice and support on healthy eating and exercise is the most effective way to reduce weight gain. Alternatively, consider switching to a drug that is less likely to cause weight gain, for example amisulpride, haloperidol, or trifluoperazine. Sedation is common with many antipsychotics (both typical and atypical). Lowering the dose may help. If sedation is still a problem, consider a switch to a less sedating drug such as amisulpride, risperidone, sulpiride or haloperidol. The person should also be advised to avoid alcohol, as this potentiates sedation. Postural hypotension can also be a problem with some drugs, particularly chlorpromazine and other phenothiazines, clozapine, quetiapine, and risperidone. It is generally dose-related. Tolerance often develops, but people with postural hypotension should be monitored carefully, as some people will still need a change in medication [Stanniland and Taylor, 2000]. Antimuscarinic adverse effects (e.g. dry mouth, blurred vision, urinary retention, constipation, and cutaneous flushing) are common with most antipsychotics, but tolerance often develops [Stanniland and Taylor, 2000]. Photosensitivity is common with chlorpromazine and other typical antipsychotics. Proper use of sunscreen will prevent sunburn in affected people. Some high-factor sun-blocks (sun protection factor 20 or above) are available on FP10. Extrapyramidal symptoms (EPS): dystonia and Parkinsonism can be alleviated by antimuscarinic drugs such as procyclidine. Antimuscarinic drugs should be withdrawn 2-3 months after symptoms resolve, as their adverse effects increase cognitive deficit. Akathisia can be relieved by reducing the dose of the antipsychotic or by co-prescribing propranolol or metoprolol [Holloman and Marder, 1997]. Alternatively, a drug that is less likely to cause EPS can be used (for example clozapine, olanzapine, or quetiapine). Low-dose risperidone (less than 6 mg per day) is also an option, but higher doses offer little or no advantage [Bazire, 2001]. Hyperprolactinaemia causes amenorrhoea, reduced fertility, galactorrhoea, sexual dysfunction, gynaecomastia, and has an increased risk of osteoporosis. Unfortunately, it seems that typical antipsychotics cause hyperprolactinaemia at doses substantially lower than those needed for therapeutic efficacy, so dose reduction is not always effective. Consider switching to quetiapine, olanzapine, or clozapine. QT interval prolongation is the most widely reported cardiac conduction defect caused by all antipsychotics. It increases the risk of torsade-de-pointes, a potentially fatal arrhythmia. Most antipsychotics have been associated with QT prolongation. Avoid co-prescribing other drugs that are known to prolong the QT interval (e.g. tricyclic antidepressants). Tardive dyskinesia (TD): the emergence of EPS is a strong risk factor for later TD. Withdrawal of antimuscarinic drugs can sometimes improve TD, and consider reducing the dose of antipsychotic. Switching to clozapine can slowly help to improve TD. Olanzapine and quetiapine are possible alternatives to clozapine. Neuroleptic malignant syndrome is a very rare, idiosyncratic, but life-threatening adverse effect that can occur with any antipsychotic. Symptoms include hyperthermia, muscle rigidity, autonomic instability, and fluctuating consciousness. The untreated mortality rate is 20%, so urgent medical treatment is needed. [Bazire, 2001; BNF 44, 2002; Stefan et al, 2002; Taylor et al, 2003] When should depot injections be considered? Consider depot injections if non-adherence is a problem, or if it is the individual's preference. Switching antipsychotics needs to be done with care, and we recommend that people be referred to specialist mental health services if a switch in dose form is needed. If depot medication is prescribed, give a test dose first - any adverse effects of a depot injection are long-lived. A small test dose is essential to avoid severe, prolonged adverse effects [Taylor et al, 2003]. If the test dose is successful, begin treatment with the lowest therapeutic dose, and administer at the longest licensed interval. Shorter intervals do not improve efficacy, and injections are painful. Since plasma levels of antipsychotics continue to fall (slowly) for a few days after the next injection, people are at most risk of clinical deterioration after an injection. In studies, relapse only seemed to occur 3-6 months after withdrawing depot treatment, which is about the time needed to clear steady-state depot drug levels from the blood [Taylor et al, 2003]. After starting depot therapy, plasma levels take several weeks to reach steady state. Doses should not, therefore, be increased for at least one month (and preferably longer) after treatment begins [Taylor et al, 2003]. Table 4. Standard doses and dose intervals for depot antipsychotic drugs. Note: lower test doses and start doses are often needed in the elderly: see British National Formulary for further details [BNF 44, 2002]. Depot injectionTest doseDose interval before standard dose givenStandard start doseLongest licensed intervalFlupentixol20 mg7 days20-40 mg4 weeksFluphenazine12.5 mg4-7 days12.5-25 mg5 weeksHaloperidol25 mg*4 weeks50 mg4 weeksPipotiazine25 mg4-7 days25-50 mg4 weeksZuclopenthixol100 mg7 days200 mg4 weeks* Test dose not stated by manufacturer [Taylor et al, 2003]Risperidone depot injection is also now available. It has a shorter maximum licensed interval than other depot injections, and must be given every 2 weeks. A test dose is not required. Orthostatic hypotension can occur, particularly after the start of treatment. Note: Risperidone depot injection must be stored in a fridge. Should people on typical antipsychotics be changed to atypicals? If a person with schizophrenia is satisfied with the drug being used, there is no need to change treatment [NICE, 2002b]. Atypical antipsychotics should be considered for people taking typical antipsychotics who: Are experiencing unacceptable adverse effects, despite adequate symptom control Have now relapsed, and did not previously get adequate symptom control from typical antipsychotics, or experienced unacceptable adverse effects The decision as to what are unacceptable adverse effects should be taken following discussion between the person with schizophrenia and the clinician responsible for treatment (for example the consultant psychiatrist) [NICE, 2002b].  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