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f e at u r e s c h i z o p h r e n i a This latest practice guidance from the Society on schizophrenia is part of a mental health toolkit which is under development. Ziba Rajaei-Dehkordi (lead author) and Denise Taylor (co-author) provide advice on pharmaceutical care services for schizophrenia. The RPSGB would like to thank all those who contributed to a mental health toolkit, including the focus group members, for their advice and expertise. Professional practice We bring you an update and the latest expert advice on dealing with patients suffering from psychosis and schizophrenia Practice Guidance: Pharmaceutical Care in Psychosis and Schizophrenia GUIDANCE OBJECTIVES • T o gain an understanding of psychosis or schizophrenia and its management • Identify pharmaceutical issues and meet patients’ needs • Explore and implement pharmaceutical care services for psychosis or schizophrenia in practice RPSGB competencies for completing a CPD entry (see appendix 6 of “Plan and Record” www.uptodate.org.uk):• “making sound decisions and solving problems in relation to drug therapy” • “promoting health and healthy lifestyles” 26 Pharmacy Professional | May 2010 May 2010 | Pharmacy Professional 27 Æ f e at u r e s c h i z o p h r e n i a This latest practice guidance from the Society on schizophrenia is part of a mental health toolkit which is under development. Ziba Rajaei-Dehkordi (lead author) and Denise Taylor (co-author) provide advice on pharmaceutical care services for schizophrenia. The RPSGB would like to thank all those who contributed to a mental health toolkit, including the focus group members, for their advice and expertise. Professional practice We bring you an update and the latest expert advice on dealing with patients suffering from psychosis and schizophrenia Practice Guidance: Pharmaceutical Care in Psychosis and Schizophrenia GUIDANCE OBJECTIVES • T o gain an understanding of psychosis or schizophrenia and its management • Identify pharmaceutical issues and meet patients’ needs • Explore and implement pharmaceutical care services for psychosis or schizophrenia in practice RPSGB competencies for completing a CPD entry (see appendix 6 of “Plan and Record” www.uptodate.org.uk):• “making sound decisions and solving problems in relation to drug therapy” • “promoting health and healthy lifestyles” 26 Pharmacy Professional | May 2010 May 2010 | Pharmacy Professional 27 Æ f e at u r e s c h i z o p h r e n i a Background Psychosis – a syndrome or a collection of symptoms, which can include delusions and hallucinations. It can be drug-induced or be part of another illness such as: schizophrenia, schizoaffective disorder, intensive psychosis or brief psychotic disorder. Schizophrenia is the best-known psychotic illness and the most common psychotic disorder. Schizophrenia is not a “split personality” but a split between the mind and reality. Schizophrenia is characterised by positive and negative symptoms (see Symptoms). The negative symptoms are less responsive to treatment with medication and are associated with decreased rates of recovery and the positive symptoms can also be very distressing to the patient. Positive and negative symptoms in schizophrenia Positive symptoms can present in a number of ways:Hallucinations Most commonly auditory command (someone telling them to do things such as jumping off a roof or to kill themselves) or olfactory. Visual and tactile are less common Delusions May be persecutory (i.e. someone is out to hurt them), religious (i.e. they believe they have religious powers or their god talks to them), grandiose (e.g. they are a celebrity; have telepathic powers), bizarre e.g. thought insertion (i.e. thoughts are put into their mind by others) or thought withdrawal (i.e. thoughts are removed from their mind) or ideas of reference (the person on the television/radio is talking just to them). Formal Thought Disorder Disorganised speech, with rapid change of topic or words put together which make no sense. Passivity Emotions, body movements or sensations are experienced as being caused by an external agency Prevalence It is a chronic mental illness affecting 1% of the population. Schizophrenia normally presents between the ages of 18 and 30, and is slightly more prevalent in males than females. Possible causes The actual cause is still unknown but the following factors may be involved:• Genetic link is strong. Children of people with schizophrenia are about 9% more likely to develop schizophrenia. • Environmental stressors such as poor maternal upbringing, deprivation in childhood, relationship problems. • Viral exposure in-utero can impair neurodevelopment and possibly lead to schizophrenia. • Drugs which may cause or exacerbate psychosis. Illicit drugs (e.g. cannabis, “magic mushrooms,” LSD, amphetamines, cocaine or ecstasy) have been implicated, and prescribed drugs (e.g. opiates, corticosteroids) can cause psychosis as a side effect Symptoms The common symptoms of psychosis: • Odd beliefs or magical thinking • Anxiety, blunted affect or depression • Irritability or loss of initiative • Low energy or poor concentration • Sleep disturbance • Social isolation and withdrawal • Perceptual disturbance • Odd thinking and speech • Odd behaviour or appearance • Paranoid ideation 28 Pharmacy Professional | May 2010 Negative symptoms lead to disturbances in social or occupational functioning. These include:Affective flattening Present as if they are depressed Alogia Poverty of speech and an inability to talk and communicate to people Avolition Inability to do anything. This can sometimes be interpreted as laziness but it is part of the illness Anhedonia Lack of ability to get pleasure from doing anything Drug-induced psychosis should be considered if delusions or hallucinations occur after the administration of a new medicine (prescribed or illicit). Treatment is generally delayed for at least 7 days to determine whether symptoms abate once the causative agent is stopped. Possible Consequences of Schizophrenia Hospitalisation: The first episode often results in hospitalisation and, of these, 20% of patients will recover fully without relapse, 20% will never fully recover and require high levels of social and medical input. More commonly, patients will partly recover but not return to baseline functioning and will suffer further relapses during their life. Suicide: The lifetime risk of people with schizophrenia committing suicide has been estimated at 10%. Type-2 diabetes predisposition: People with schizophrenia are 2 to 4 times more likely to develop type 2 diabetes than those who are not. The actual prevalence of type 2 diabetes in people with schizophrenia is between 15 and 18%, but the prevalence of impaired glucose tolerance may be as high as 30% depending on age. Treatment The NICE Clinical Guideline for schizophrenia http://guidance.nice.org. uk/CG82 outlines a holistic approach to patient care including pharmacological and non-pharmacological interventions. It is an important consideration that medication forms only part of the overall care package for people with schizophrenia and that supported adherence interventions can improve long-term outcomes in patient care. Non-Pharmacological • Talking therapy such as problem-solving therapy, • Cognitive behavioural therapy, • Family therapy and support with social integration, • Psychotherapy is recommended if there is a history of psychological and physical abuse, • Patient support groups such as ‘Hearing Voices’; supports people to live with auditory hallucinations. Pharmacological There are two groups of antipsychotics used to treat schizophrenia:• Typical (or first generation) and • Atypical (or second generation) agents. Their main mode of action is to block dopamine pathways in the brain, and 5H2 blockade (atypical antipsychotics). For further information See Practice Guidance: Supporting Patients on Antipsychotics Pregnancy and Breastfeeding – Specialist input is required to support women who are planning pregnancy or have become pregnant during treatment, or wish to breastfeed. Practice Points for Pharmacists • Encourage and support patients to undertake activities and address lifestyle issues, to promote good mental. Signpost to local and/or national support resources. • Drug-induced psychosis – if suspected refer for medical review to either the prescriber, GP or local mental healthcare team. • Poorly compliant patients may benefit from a once daily preparation and/or use of compliance aids. • Recognition of persistent side effects requiring support and/or advice and/or referral for clinical review. • Check for interactions, including OTC remedies. See BNF www.bnf.org • Patients at risk of suicide require urgent referral to a crisis resolution team or psychiatric emergency services or Accident and Emergency Department or GP. • Poisoning by antipsychotic drugs requires immediate referral to doctor. Features include convulsions, extrapyramidal symptoms and hypotension. • Clozapine • Signs of infection, temperature and sore throat require immediate patient reporting to doctor. Explain to patient that they are likely to need an additional blood test. • Caffeine increases and smoking decreases plasma clozapine levels. Advice on clozapine dose should be sought from prescriber if there are any changes in caffeine intake or smoking status. • Clozapine (and olanzapine) can cause up to 10 to 15kg weight gain. Advise patients about healthy eating and exercise. • Missed doses: if a patient misses medication for 2 days then clozapine needs to be re-initiated. Continuing with the same dose without re-initiation can result in cardiovascular effects. Refer urgently • Chlorpromazine warning - Owing to the risk of contact dermatitis, avoid direct contact with chlorpromazine; (tablets should not be crushed and solutions should be handled with care) • Photosensitivity can occur with chlorpromazine. Advise patient to wear sun protection in the sun. Levels of Pharmaceutical Care Services for Supporting People with psychosis and schizophrenia In general pharmacists can: Recognise possible symptoms of schizophrenia/psychosis especially when responding to symptoms and refer as appropriate Identify people possibly at risk of schizophrenia/psychosis and refer appropriately. Signpost people to support groups and information on pharmacological and nonpharmacological treatments Level 1: Pharmacists can: Provide a medication review service, with a key focus to support any adherence problems:• Identify new patients by prescription (ensure understanding of illness, its treatment and available support including information on adverse effects, concordance, diet and exercise and support groups) • Be aware of concomitant medicines that may cause or exacerbate psychosis • Identify any pharmaceutical issues (interactions including OTC medication, alcohol and smoking). Pharmacists can offer support for healthy lifestyle interventions Level 2: Pharmacists can: Recognise symptoms of relapse: e.g. self-neglect; poor speech and ability to concentrate or interact with others; strange thoughts or behaviour. Referral to the appropriate care team, or, following a preset agreement for how the patient wishes to be managed in relapse, and who should be contacted. Pharmacists can offer support for healthy lifestyle interventions, including:• Smoking cessation - Be aware that smoking reduces clozapine levels resulting in a need to increase dosages; if a person on clozapine stops smoking make urgent referral for blood monitoring and dosage review • Use of alcohol NHS Choices: Live well cut down on alcohol http://www.nhs.uk/ Livewell/Alcohol/Pages/Alcoholhome. aspx • Diet and exercise support and advice. Top Tips for eating more fruit and vegetable http://www.5aday.nhs.uk/topTips/default. html • Sleep hygiene advice and support • Vascular risk and weight management. Patients with psychosis and schizophrenia are more likely to develop diabetes due to the risk of antipsychotics causing weight gain. Level 3: Specialist Mental Health Level; Pharmacists role in effective care for those with chronic psychotic illness Pharmacists can: • Provide medicine education sessions • Monitor response and side effects • Suggest therapeutic changes if poor response • Prescribe (if appropriately trained and qualified) in collaboration with healthcare team and Community Mental Health Team (CMHT) if appropriate • Provide (if appropriately trained and qualified) a basic talking therapy service e.g. cognitive based therapy, mindfulness training • Provide clozapine dispensing services in the community. May 2010 | Pharmacy Professional 29 Æ f e at u r e s c h i z o p h r e n i a Background Psychosis – a syndrome or a collection of symptoms, which can include delusions and hallucinations. It can be drug-induced or be part of another illness such as: schizophrenia, schizoaffective disorder, intensive psychosis or brief psychotic disorder. Schizophrenia is the best-known psychotic illness and the most common psychotic disorder. Schizophrenia is not a “split personality” but a split between the mind and reality. Schizophrenia is characterised by positive and negative symptoms (see Symptoms). The negative symptoms are less responsive to treatment with medication and are associated with decreased rates of recovery and the positive symptoms can also be very distressing to the patient. Positive and negative symptoms in schizophrenia Positive symptoms can present in a number of ways:Hallucinations Most commonly auditory command (someone telling them to do things such as jumping off a roof or to kill themselves) or olfactory. Visual and tactile are less common Delusions May be persecutory (i.e. someone is out to hurt them), religious (i.e. they believe they have religious powers or their god talks to them), grandiose (e.g. they are a celebrity; have telepathic powers), bizarre e.g. thought insertion (i.e. thoughts are put into their mind by others) or thought withdrawal (i.e. thoughts are removed from their mind) or ideas of reference (the person on the television/radio is talking just to them). Formal Thought Disorder Disorganised speech, with rapid change of topic or words put together which make no sense. Passivity Emotions, body movements or sensations are experienced as being caused by an external agency Prevalence It is a chronic mental illness affecting 1% of the population. Schizophrenia normally presents between the ages of 18 and 30, and is slightly more prevalent in males than females. Possible causes The actual cause is still unknown but the following factors may be involved:• Genetic link is strong. Children of people with schizophrenia are about 9% more likely to develop schizophrenia. • Environmental stressors such as poor maternal upbringing, deprivation in childhood, relationship problems. • Viral exposure in-utero can impair neurodevelopment and possibly lead to schizophrenia. • Drugs which may cause or exacerbate psychosis. Illicit drugs (e.g. cannabis, “magic mushrooms,” LSD, amphetamines, cocaine or ecstasy) have been implicated, and prescribed drugs (e.g. opiates, corticosteroids) can cause psychosis as a side effect Symptoms The common symptoms of psychosis: • Odd beliefs or magical thinking • Anxiety, blunted affect or depression • Irritability or loss of initiative • Low energy or poor concentration • Sleep disturbance • Social isolation and withdrawal • Perceptual disturbance • Odd thinking and speech • Odd behaviour or appearance • Paranoid ideation 28 Pharmacy Professional | May 2010 Negative symptoms lead to disturbances in social or occupational functioning. These include:Affective flattening Present as if they are depressed Alogia Poverty of speech and an inability to talk and communicate to people Avolition Inability to do anything. This can sometimes be interpreted as laziness but it is part of the illness Anhedonia Lack of ability to get pleasure from doing anything Drug-induced psychosis should be considered if delusions or hallucinations occur after the administration of a new medicine (prescribed or illicit). Treatment is generally delayed for at least 7 days to determine whether symptoms abate once the causative agent is stopped. Possible Consequences of Schizophrenia Hospitalisation: The first episode often results in hospitalisation and, of these, 20% of patients will recover fully without relapse, 20% will never fully recover and require high levels of social and medical input. More commonly, patients will partly recover but not return to baseline functioning and will suffer further relapses during their life. Suicide: The lifetime risk of people with schizophrenia committing suicide has been estimated at 10%. Type-2 diabetes predisposition: People with schizophrenia are 2 to 4 times more likely to develop type 2 diabetes than those who are not. The actual prevalence of type 2 diabetes in people with schizophrenia is between 15 and 18%, but the prevalence of impaired glucose tolerance may be as high as 30% depending on age. Treatment The NICE Clinical Guideline for schizophrenia http://guidance.nice.org. uk/CG82 outlines a holistic approach to patient care including pharmacological and non-pharmacological interventions. It is an important consideration that medication forms only part of the overall care package for people with schizophrenia and that supported adherence interventions can improve long-term outcomes in patient care. Non-Pharmacological • Talking therapy such as problem-solving therapy, • Cognitive behavioural therapy, • Family therapy and support with social integration, • Psychotherapy is recommended if there is a history of psychological and physical abuse, • Patient support groups such as ‘Hearing Voices’; supports people to live with auditory hallucinations. Pharmacological There are two groups of antipsychotics used to treat schizophrenia:• Typical (or first generation) and • Atypical (or second generation) agents. Their main mode of action is to block dopamine pathways in the brain, and 5H2 blockade (atypical antipsychotics). For further information See Practice Guidance: Supporting Patients on Antipsychotics Pregnancy and Breastfeeding – Specialist input is required to support women who are planning pregnancy or have become pregnant during treatment, or wish to breastfeed. Practice Points for Pharmacists • Encourage and support patients to undertake activities and address lifestyle issues, to promote good mental. Signpost to local and/or national support resources. • Drug-induced psychosis – if suspected refer for medical review to either the prescriber, GP or local mental healthcare team. • Poorly compliant patients may benefit from a once daily preparation and/or use of compliance aids. • Recognition of persistent side effects requiring support and/or advice and/or referral for clinical review. • Check for interactions, including OTC remedies. See BNF www.bnf.org • Patients at risk of suicide require urgent referral to a crisis resolution team or psychiatric emergency services or Accident and Emergency Department or GP. • Poisoning by antipsychotic drugs requires immediate referral to doctor. Features include convulsions, extrapyramidal symptoms and hypotension. • Clozapine • Signs of infection, temperature and sore throat require immediate patient reporting to doctor. Explain to patient that they are likely to need an additional blood test. • Caffeine increases and smoking decreases plasma clozapine levels. Advice on clozapine dose should be sought from prescriber if there are any changes in caffeine intake or smoking status. • Clozapine (and olanzapine) can cause up to 10 to 15kg weight gain. Advise patients about healthy eating and exercise. • Missed doses: if a patient misses medication for 2 days then clozapine needs to be re-initiated. Continuing with the same dose without re-initiation can result in cardiovascular effects. Refer urgently • Chlorpromazine warning - Owing to the risk of contact dermatitis, avoid direct contact with chlorpromazine; (tablets should not be crushed and solutions should be handled with care) • Photosensitivity can occur with chlorpromazine. Advise patient to wear sun protection in the sun. Levels of Pharmaceutical Care Services for Supporting People with psychosis and schizophrenia In general pharmacists can: Recognise possible symptoms of schizophrenia/psychosis especially when responding to symptoms and refer as appropriate Identify people possibly at risk of schizophrenia/psychosis and refer appropriately. Signpost people to support groups and information on pharmacological and nonpharmacological treatments Level 1: Pharmacists can: Provide a medication review service, with a key focus to support any adherence problems:• Identify new patients by prescription (ensure understanding of illness, its treatment and available support including information on adverse effects, concordance, diet and exercise and support groups) • Be aware of concomitant medicines that may cause or exacerbate psychosis • Identify any pharmaceutical issues (interactions including OTC medication, alcohol and smoking). Pharmacists can offer support for healthy lifestyle interventions Level 2: Pharmacists can: Recognise symptoms of relapse: e.g. self-neglect; poor speech and ability to concentrate or interact with others; strange thoughts or behaviour. Referral to the appropriate care team, or, following a preset agreement for how the patient wishes to be managed in relapse, and who should be contacted. Pharmacists can offer support for healthy lifestyle interventions, including:• Smoking cessation - Be aware that smoking reduces clozapine levels resulting in a need to increase dosages; if a person on clozapine stops smoking make urgent referral for blood monitoring and dosage review • Use of alcohol NHS Choices: Live well cut down on alcohol http://www.nhs.uk/ Livewell/Alcohol/Pages/Alcoholhome. aspx • Diet and exercise support and advice. Top Tips for eating more fruit and vegetable http://www.5aday.nhs.uk/topTips/default. html • Sleep hygiene advice and support • Vascular risk and weight management. Patients with psychosis and schizophrenia are more likely to develop diabetes due to the risk of antipsychotics causing weight gain. Level 3: Specialist Mental Health Level; Pharmacists role in effective care for those with chronic psychotic illness Pharmacists can: • Provide medicine education sessions • Monitor response and side effects • Suggest therapeutic changes if poor response • Prescribe (if appropriately trained and qualified) in collaboration with healthcare team and Community Mental Health Team (CMHT) if appropriate • Provide (if appropriately trained and qualified) a basic talking therapy service e.g. cognitive based therapy, mindfulness training • Provide clozapine dispensing services in the community. May 2010 | Pharmacy Professional 29 Æ f e at u r e s c h i z o p h r e n i a Practice Guidance: Supporting Patients on Antipsychotics GUIDANCE OBJECTIVES To understand, identify and meet the pharmaceutical care needs of patients:• initiating antipsychotic therapy • on maintenance therapy, and • withdrawing from antipsychotic therapy RPSGB competencies for completing a CPD entry (see appendix 6 of “Plan and Record” www.uptodate.org.uk):“making sound decisions and solving problems in relation to drug therapy” “promoting health and healthy lifestyles” Background Antipsychotic drugs are also known as ‘neuroleptics’ and (misleadingly) as ‘major tranquillisers’. Antipsychotic drugs generally tranquillise without impairing consciousness and without causing paradoxical excitement but they should not be regarded merely as tranquillisers. For conditions such as schizophrenia the tranquillising effect is of secondary importance. 1.Pharmaceutical Care at Initiation People presenting for the first time with psychosis will generally be initiated treatment in a secondary care setting. It is recommended that the potential side effects are discussed with the patient at the point of prescribing, to ensure the optimal choice of medication is aligned with the patient’s lifestyle. Advice to patients at Initiation • Possible side effects (see Side effects) All can cause side effects; people should be made aware that these medicines may make them feel worse (due to side effects) before they start to feel better. • Time to onset of action usually has an effect in a few days, with effect building over 3-4 weeks • Take at a regular time each day • Possible withdrawal effects Do not to stop taking suddenly as may experience a withdrawal syndrome. (see Pharmaceutical Care on Withdrawal section) • Drowsiness may affect performance of skilled tasks (e.g. driving or operating machinery), especially at start of treatment; effects of alcohol are enhanced. • Avoid alcohol (Alcohol is a CNS depressant; can also increase sedative side effects of antipsychotics) 30 Pharmacy Professional | May 2010 • Provide information and signpost: - Leaflets on psychosis/schizophrenia and medication - Support resources e.g. audiotapes, peer support groups, including diet and lifestyle Antipsychotic side effect profiles Antipsychotic drugs are considered to act by interfering with dopaminergic transmission in the brain by blocking dopamine D2 receptors, which may give rise to the extrapyramidal effects, and also to hyperprolactinaemia. Extrapyramidal effects and hyperprolactinaemia are less common with atypical antipsychotics. Antipsychotics also interact with a number of other receptor systems such as histamine receptors, alpha-receptors and muscarinic receptors resulting in a range of different side effects (e.g. weight gain; postural hypotension and drowsiness respectively). Typical Antipsychotics Extrapyramidal symptoms (EPSE) are the most troublesome. They are easy to recognise but cannot be predicted accurately because they depend on the dose, the type of drug, and on individual susceptibility. The relative incidence of EPSE is as follows:Most likely Moderately likely Least likely Fluphenazine, perphenazine, trifluoperazine, zuclopenthixol and haloperidol Flupentixol, pipotiazine Chlorpromazine, levomepromazine Pericyazine, sulpiride Atypical Antipsychotics Clinically less likely to cause extrapyramidal side effects including tardive dyskinesia, or to affect prolactin levels. There is an increased risk of developing or exacerbating diabetes with all antipsychotics but especially some atypical antipsychotics (e.g. clozapine, olanzapine and quetiapine). Clozapine has proven benefit in treating associated negative symptoms of schizophrenia. Aripiprazole, clozapine, olanzapine, quetiapine, cause little or no elevation of prolactin levels. Side Effects: Advice on Management Clozapine used in ‘treatment resistant’ schizophrenia, can cause blood dyscrasias. Its use is restricted to patients registered with a clozapine monitoring service (see Clozapine Monitoring). Medication Presenting signs and symptoms Considerations & Advice Extrapyramidal Parkinsonism Approximately 20% of patients treated with typical antipsychotics will develop the parkinsonism side effect of rigidity, tremor, akinesia (lack of movement) and bradykinesia (slowness of movement). Onset is usually within days or weeks of treatment. Patient’s medication to be reviewed with their doctor, potential management options of:Reducing dose of antipsychotic Prescribing an anticholinergic Switching to an atypical antipsychotic Side Effects: Advice on Management People need to be informed about the most common side effects to self manage and identify when to seek urgent medical advice. Akathisia (restlessness) Common in over 25% of patients with typical antipsychotics, characteristically occurs after large initial doses and may resemble an exacerbation of the condition being treated. Refer to doctor For a detailed list of side effects see BNF www.bnf.org Dystonia (group of muscles go into spasm (e.g torticollis (neck) oculogyria (eyes)) 90% cases of occur in the first 5 days of treatment. Up to 10% of patients treated with typical antipsychotics will develop dystonia in one form or another. Immediate medical attention is required – with administration an anticholinergic and/or change to an atypical antipsychotic >> See table opposite Interactions: prevention and advice For interactions see BNF www.bnf.org Key considerations: • Metabolism by the cytochrome P450 system: Blood levels of antipsychotics can be affected by concomitantly prescribed medicines which undergo the same metabolic pathway. Check for interactions at all times. Tardive Dyskinesia (rhythmic, involuntary movements of tongue, face, & jaw) Develop over months or even years following chronic exposure to antipsychotics or with high dosage. May resolve (up to 6 months) by stopping the drug, but in some cases it is irreversible. Atypical antipsychotics are thought to have a lower risk. Refer to doctor. Hormonal – hyperprolactinaemia e.g. Patient on clozapine prescribed erythromycin; may increase clozapine levels and induce adverse effects such as seizure • Immunosupression can occur with some antipsychotics, e.g. clozapine and chlorpromazine. Use with caution and monitor patient when co-prescribed with myelosuppressive agents. Regular blood monitoring is mandatory for clozapine. Risks of sudden death: Generally only one antipsychotic at a time should be prescribed; exceptions are when stopping one and starting another, or if a depot is being prescribed and there are breakthrough symptoms. Risks include sudden death (especially if doses are above BNF limits) and Neuroleptic Malignant Syndrome (NMS). NMS is rare (in approximately 1% of patients treated with antipsychotics), but potentially fatal and should be treated as a medical emergency. Signs & Symptoms of NMS Severe muscle rigidity and elevated temperature with two of the following: tremor; diaphoresis, dysphagia, incontinence, changes in consciousness, mutism, tachycardia, increased blood pressure. Typical antipsychotics and some atypicals (e.g. risperidone) may cause increased levels of prolactin, which can cause a number of symptoms such as gynaecomastia (breast enlargement) and galactorrhoea (secreting breast milk), increased risk of osteoporosis, menstrual and sexual dysfunction, acne and hirsutism. Counselling Point: Women of childbearing age may need contraceptive advice when switching from a typical to an atypical antipsychotic. Cardiovascular – Hypotention, arrhythmias and sudden death Postural hypotension and arrhythmias with some antipsychotics (especially during initial dose titration). Clozapine: Fatal myocarditis (most commonly in first 2 months) and cardiomyopathy reported. Refer to doctor if present with cardiovascular symptoms Antimuscarinic Symptoms such as dry mouth, constipation, difficulty with micturition, and blurred vision. Advise as appropriate Blood dyscrasias Clozapine has the greatest risk of causing neutropenia and agranulocytosis; not dose-related. Can occur at any time, but the first 18 weeks are considered the period of highest risk. See clozapine monitoring below. Hyperlipidaemia Can occur with any antipsychotic. Advise and support, provide cholesterol testing Diabetes Antipsychotics, particularly some atypicals have been associated with increased risk of hyperglycaemia and development of diabetes. Recognise potential signs and symptoms, advise and support, provide glucose testing Weight gain Associated with all antipsychotic medication. Provide weight monitoring and management support and advice Clozapine Monitoring Monitoring is essential due to risk of blood dyscrasias (usually reversible neutropenia in 3-4% patients, which may progress to agranulocytosis in 0.8% patients over one year). Patients MUST be registered with a clozapine patient monitoring service. • A full blood count must be performed weekly for 18 weeks, fortnightly up to 52 weeks and 4-weekly thereafter and 4 weeks after discontinuation. Other monitoring: • Check for interactions: concomitant medication, caffeine ingestion and smoking affects clozapine blood levels. Report potential interactions to Doctor immediately. • Caution if used with drugs which cause constipation (e.g. antimuscarinic drugs) or in history of colonic disease or bowel surgery. Monitor for constipation and refer to doctor or advise on laxative if required. • Signs of infection, temperature and sore throat require immediate patient reporting to doctor. (Usually an additional blood test is taken). 2.Pharmaceutical Care for Maintenance People prescribed antipsychotics are at risk of weight gain, metabolic malignant syndrome and potentially type 2-diabetes. Diabetes is an independent risk factor for cardiovascular disease; therefore monitoring and support should include the following: Weight gain: provide advice on healthy eating and weight management Diabetes and Cardiovascular risk Lifestyle issues: promote good mental & physical health Switching antipsychotics due to inadequate efficacy Switching is generally achieved by gradual reduction of the dose of the first agent and simultaneous titration up of the second agent (cross-tapering). For further advice see the BNF www.bnf. org, Psychotropic Drug Directory and the Maudsley Prescribing Guidelines 3.Pharmaceutical Care on Withdrawal When stopped suddenly, antipsychotics may produce an acute withdrawal syndrome in some people. Rapid relapse can also occur. Withdrawal of antipsychotic agents after longterm therapy should always be gradual and the patient should be closely monitored for signs of relapse or discontinuation symptoms. May 2010 | Pharmacy Professional 31 Æ f e at u r e s c h i z o p h r e n i a Practice Guidance: Supporting Patients on Antipsychotics GUIDANCE OBJECTIVES To understand, identify and meet the pharmaceutical care needs of patients:• initiating antipsychotic therapy • on maintenance therapy, and • withdrawing from antipsychotic therapy RPSGB competencies for completing a CPD entry (see appendix 6 of “Plan and Record” www.uptodate.org.uk):“making sound decisions and solving problems in relation to drug therapy” “promoting health and healthy lifestyles” Background Antipsychotic drugs are also known as ‘neuroleptics’ and (misleadingly) as ‘major tranquillisers’. Antipsychotic drugs generally tranquillise without impairing consciousness and without causing paradoxical excitement but they should not be regarded merely as tranquillisers. For conditions such as schizophrenia the tranquillising effect is of secondary importance. 1.Pharmaceutical Care at Initiation People presenting for the first time with psychosis will generally be initiated treatment in a secondary care setting. It is recommended that the potential side effects are discussed with the patient at the point of prescribing, to ensure the optimal choice of medication is aligned with the patient’s lifestyle. Advice to patients at Initiation • Possible side effects (see Side effects) All can cause side effects; people should be made aware that these medicines may make them feel worse (due to side effects) before they start to feel better. • Time to onset of action usually has an effect in a few days, with effect building over 3-4 weeks • Take at a regular time each day • Possible withdrawal effects Do not to stop taking suddenly as may experience a withdrawal syndrome. (see Pharmaceutical Care on Withdrawal section) • Drowsiness may affect performance of skilled tasks (e.g. driving or operating machinery), especially at start of treatment; effects of alcohol are enhanced. • Avoid alcohol (Alcohol is a CNS depressant; can also increase sedative side effects of antipsychotics) 30 Pharmacy Professional | May 2010 • Provide information and signpost: - Leaflets on psychosis/schizophrenia and medication - Support resources e.g. audiotapes, peer support groups, including diet and lifestyle Antipsychotic side effect profiles Antipsychotic drugs are considered to act by interfering with dopaminergic transmission in the brain by blocking dopamine D2 receptors, which may give rise to the extrapyramidal effects, and also to hyperprolactinaemia. Extrapyramidal effects and hyperprolactinaemia are less common with atypical antipsychotics. Antipsychotics also interact with a number of other receptor systems such as histamine receptors, alpha-receptors and muscarinic receptors resulting in a range of different side effects (e.g. weight gain; postural hypotension and drowsiness respectively). Typical Antipsychotics Extrapyramidal symptoms (EPSE) are the most troublesome. They are easy to recognise but cannot be predicted accurately because they depend on the dose, the type of drug, and on individual susceptibility. The relative incidence of EPSE is as follows:Most likely Moderately likely Least likely Fluphenazine, perphenazine, trifluoperazine, zuclopenthixol and haloperidol Flupentixol, pipotiazine Chlorpromazine, levomepromazine Pericyazine, sulpiride Atypical Antipsychotics Clinically less likely to cause extrapyramidal side effects including tardive dyskinesia, or to affect prolactin levels. There is an increased risk of developing or exacerbating diabetes with all antipsychotics but especially some atypical antipsychotics (e.g. clozapine, olanzapine and quetiapine). Clozapine has proven benefit in treating associated negative symptoms of schizophrenia. Aripiprazole, clozapine, olanzapine, quetiapine, cause little or no elevation of prolactin levels. Side Effects: Advice on Management Clozapine used in ‘treatment resistant’ schizophrenia, can cause blood dyscrasias. Its use is restricted to patients registered with a clozapine monitoring service (see Clozapine Monitoring). Medication Presenting signs and symptoms Considerations & Advice Extrapyramidal Parkinsonism Approximately 20% of patients treated with typical antipsychotics will develop the parkinsonism side effect of rigidity, tremor, akinesia (lack of movement) and bradykinesia (slowness of movement). Onset is usually within days or weeks of treatment. Patient’s medication to be reviewed with their doctor, potential management options of:Reducing dose of antipsychotic Prescribing an anticholinergic Switching to an atypical antipsychotic Side Effects: Advice on Management People need to be informed about the most common side effects to self manage and identify when to seek urgent medical advice. Akathisia (restlessness) Common in over 25% of patients with typical antipsychotics, characteristically occurs after large initial doses and may resemble an exacerbation of the condition being treated. Refer to doctor For a detailed list of side effects see BNF www.bnf.org Dystonia (group of muscles go into spasm (e.g torticollis (neck) oculogyria (eyes)) 90% cases of occur in the first 5 days of treatment. Up to 10% of patients treated with typical antipsychotics will develop dystonia in one form or another. Immediate medical attention is required – with administration an anticholinergic and/or change to an atypical antipsychotic >> See table opposite Interactions: prevention and advice For interactions see BNF www.bnf.org Key considerations: • Metabolism by the cytochrome P450 system: Blood levels of antipsychotics can be affected by concomitantly prescribed medicines which undergo the same metabolic pathway. Check for interactions at all times. Tardive Dyskinesia (rhythmic, involuntary movements of tongue, face, & jaw) Develop over months or even years following chronic exposure to antipsychotics or with high dosage. May resolve (up to 6 months) by stopping the drug, but in some cases it is irreversible. Atypical antipsychotics are thought to have a lower risk. Refer to doctor. Hormonal – hyperprolactinaemia e.g. Patient on clozapine prescribed erythromycin; may increase clozapine levels and induce adverse effects such as seizure • Immunosupression can occur with some antipsychotics, e.g. clozapine and chlorpromazine. Use with caution and monitor patient when co-prescribed with myelosuppressive agents. Regular blood monitoring is mandatory for clozapine. Risks of sudden death: Generally only one antipsychotic at a time should be prescribed; exceptions are when stopping one and starting another, or if a depot is being prescribed and there are breakthrough symptoms. Risks include sudden death (especially if doses are above BNF limits) and Neuroleptic Malignant Syndrome (NMS). NMS is rare (in approximately 1% of patients treated with antipsychotics), but potentially fatal and should be treated as a medical emergency. Signs & Symptoms of NMS Severe muscle rigidity and elevated temperature with two of the following: tremor; diaphoresis, dysphagia, incontinence, changes in consciousness, mutism, tachycardia, increased blood pressure. Typical antipsychotics and some atypicals (e.g. risperidone) may cause increased levels of prolactin, which can cause a number of symptoms such as gynaecomastia (breast enlargement) and galactorrhoea (secreting breast milk), increased risk of osteoporosis, menstrual and sexual dysfunction, acne and hirsutism. Counselling Point: Women of childbearing age may need contraceptive advice when switching from a typical to an atypical antipsychotic. Cardiovascular – Hypotention, arrhythmias and sudden death Postural hypotension and arrhythmias with some antipsychotics (especially during initial dose titration). Clozapine: Fatal myocarditis (most commonly in first 2 months) and cardiomyopathy reported. Refer to doctor if present with cardiovascular symptoms Antimuscarinic Symptoms such as dry mouth, constipation, difficulty with micturition, and blurred vision. Advise as appropriate Blood dyscrasias Clozapine has the greatest risk of causing neutropenia and agranulocytosis; not dose-related. Can occur at any time, but the first 18 weeks are considered the period of highest risk. See clozapine monitoring below. Hyperlipidaemia Can occur with any antipsychotic. Advise and support, provide cholesterol testing Diabetes Antipsychotics, particularly some atypicals have been associated with increased risk of hyperglycaemia and development of diabetes. Recognise potential signs and symptoms, advise and support, provide glucose testing Weight gain Associated with all antipsychotic medication. Provide weight monitoring and management support and advice Clozapine Monitoring Monitoring is essential due to risk of blood dyscrasias (usually reversible neutropenia in 3-4% patients, which may progress to agranulocytosis in 0.8% patients over one year). Patients MUST be registered with a clozapine patient monitoring service. • A full blood count must be performed weekly for 18 weeks, fortnightly up to 52 weeks and 4-weekly thereafter and 4 weeks after discontinuation. Other monitoring: • Check for interactions: concomitant medication, caffeine ingestion and smoking affects clozapine blood levels. Report potential interactions to Doctor immediately. • Caution if used with drugs which cause constipation (e.g. antimuscarinic drugs) or in history of colonic disease or bowel surgery. Monitor for constipation and refer to doctor or advise on laxative if required. • Signs of infection, temperature and sore throat require immediate patient reporting to doctor. (Usually an additional blood test is taken). 2.Pharmaceutical Care for Maintenance People prescribed antipsychotics are at risk of weight gain, metabolic malignant syndrome and potentially type 2-diabetes. Diabetes is an independent risk factor for cardiovascular disease; therefore monitoring and support should include the following: Weight gain: provide advice on healthy eating and weight management Diabetes and Cardiovascular risk Lifestyle issues: promote good mental & physical health Switching antipsychotics due to inadequate efficacy Switching is generally achieved by gradual reduction of the dose of the first agent and simultaneous titration up of the second agent (cross-tapering). For further advice see the BNF www.bnf. org, Psychotropic Drug Directory and the Maudsley Prescribing Guidelines 3.Pharmaceutical Care on Withdrawal When stopped suddenly, antipsychotics may produce an acute withdrawal syndrome in some people. Rapid relapse can also occur. Withdrawal of antipsychotic agents after longterm therapy should always be gradual and the patient should be closely monitored for signs of relapse or discontinuation symptoms. May 2010 | Pharmacy Professional 31 Æ f e at u r e s c h i z o p h r e n i a Patient Resources and Support Groups Useful Resources for Pharmacists • MIND www.mind.org.uk • Mental Health Foundation www.mentalhealth.org.uk • Rethink www.rethink.org • Patient UK www.patient.co.uk/selfhelp.asp • Choice and Medication www.choiceandmedication.org.uk • Hearing Voices www.hearing-voices.org • Saneline www.saneline.org.uk • PharmacyHealthLink Lifestyle resources (“resource cards”, leaflets, posters): www. pharmacyhealthlink.org.uk/?q=leaflets-andfactsheets • Lifestyle www.nhs.uk/livewell/Pages/ Livewellhub.aspx (weight loss, alcohol, smoking, sleep, mental health etc.) • Department of Health ‘Choosing talking therapies?’ www.dh.gov.uk/en/ Publicationsandstatistics/Publications/ PublicationsPolicyAndGuidance/DH_4008162 • Mental Health Foundation Talking therapies www.mentalhealth.org.uk/information/mentalhealth-a-z/talking-therapies/ • United Kingdom Psychiatric Pharmacy Group www.ukppg.org.uk • Bazire S. Psychotropic Drug Directory 2009. Aberdeen: HealthComm UK Ltd; 2009 • Taylor D, Paton C, Shitij K. The Maudsley Prescribing Guidelines 10th Edition. London: Informa Healthcare; 2009 • Francis SA, Patel M. Caring for people with schizophrenia: family carers’ involvement with medication. Int J Pharm Pract. 2000:8:314-23 • Bleakey S, Weatherill M. Treatments for patients with schizophrenia. Pharmaceutical Journal 2009:283:101-104 (July 25) www.pjonline.com • Khan S. Getting ready for NHS Health Checks. Pharmaceutical Journal 2009:282:417-418 (Apr 11) www.pjonline.com • RPSGB Practice guidance: obesity www.rpsgb.org/pdfs/ obesityguid.pdf • Neuroleptic Malignant Syndrome: www.nmsis.org 32 Pharmacy Professional | May 2010 Pregnancy and Breastfeeding • UKMI www.ukmi.nhs.uk/default.asp advert