-Guidelines for the discontinuation of oral antipsychotics in patients with BPSD within the primary care setting Summary- Quetiapine An independent report Time for action 1 by Professor Sube Banerjee looked at the prescribing of antipsychotics in people with dementia and highlighted an unacceptable level of people with dementia dying as a result of being prescribed an antipsychotic. It recommended limiting the use of low dose antipsychotics for when symptoms are severe, distressing, and create risk to the patient or others and non-pharmacological approaches have been tried and failed. NICE Quality Standards for Dementia focuses on non-cognitive symptoms and behaviour that challenges and makes clear that a goal of 0% should be set for antipsychotic use in people with mild-to-moderate noncognitive symptoms. 2 The Department of Health aims to support local areas to prescribe appropriately with a view to achieving overall a two-thirds reduction in the use of antipsychotic medicines over a period of two years from establishing a baseline position. 3 A call to action asks that people with dementia who are receiving antipsychotic drugs should receive a clinical review from their doctor to ensure that their care is compliant with current best practice and guidelines, and that alternatives to medication have been considered by 31 March 2012. 4 Significant side effects 5 In 1000 patients treated for 12 weeks with an atypical antipsychotic there will be: 10 additional deaths 18 extra cerebrovascular events (half of them severe) 58-94 patients with gait disturbance 167 extra deaths when treated over 2 years Number needed to harm = 6 when given for over 2 years. Efficacy Improvement in BPSD seen in up to 20% of patients treated. 6 The Alzheimer s Society advises that at least 30% of antipsychotic prescriptions could be reduced or stopped without any ill effects and that 70% of people have no worsening of symptoms when antipsychotics are discontinued. 7 Risk factors Highlight patients who are potentially at a higher risk of cerebrovascular disease for a priority review: over 80 years of age (highest risk) any previous history of stroke or TIA hypertension diabetes currently smoking atrial fibrillation 1 http://www.dh.gov.uk/dr_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108302.pdf 2 http://www.nice.org.uk/media/7ef/3f/dementiaqualitystandard.pdf 3 http://www.dementia.dh.gov.uk/_library/web_version_-_final_- Refresh_Implementation_Plan_27.pdf 4 http://www.dh.gov.uk/en/aboutus/features/dh_127440 5 Dementia Collaborative-Learning Series One 26.05.11 6 http://www.dh.gov.uk/dr_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108302.pdf 7 http://www.alzheimers.org.uk/antipsychotics Page 1 of 8
Discontinuation: Unless there is severe risk or extreme distress the recommended default management is to discontinue the antipsychotic and monitor/assess using watchful waiting and specific interventions under PAIN or other interventions. If further treatment with antipsychotics is clinically necessary after 12 weeks then a referral to specialist services is advised (DAA, RCGP, DH). 8 Undertake a thorough risk/ benefit analysis for each individual patient and document in the patient record. Due to the increased cerebrovascular and mortality risks in patients aged 65 years and over, antipsychotics should not be prescribed for more than 3 months in BPSD without sound reasons, which should be documented 9. If patient had schizophrenia with psychosis prior to BPSD then this may be a good reason to continue prescribing beyond 3 months. Recurrence of BPSD may be more likely if previous discontinuation has caused symptoms to return or the person currently has severe symptoms. 10 Consider the following factors: Are there any symptoms from the agreed criteria and if now symptom free, for how long? Are there any adverse effects and how severe are they? How severe were the symptoms, what was the speed of onset, duration and was there any danger to the patient or others from the symptoms? Has dosage reduction been already been tried and what was the result? What are the physical and social circumstances of the patient and are they likely to exacerbate a relapse? What is the potential social cost of a relapse? e.g. carer unable to cope. Is the patient/carer/family able to monitor symptoms and contact a healthcare professional if there is a relapse? Abrupt withdrawal when on high doses may lead to discontinuation symptoms in some patients and should be avoided unless there is a severe adverse reaction. For low doses discontinuation symptoms are unlikely and so they can be stopped with careful monitoring. Withdrawal after long-term therapy on higher doses should be gradual and closely monitored. For relapse start the BPSD patient treatment algorithm in the BPSD guidelines again as symptoms and risks may have changed. 8 http://www.alzheimers.org.uk/antipsychotics 9 http://www.mhra.gov.uk/safetyinformation/generalsafetyinformationandadvice/product-specificinformationandadvice/antipsychoticdrugs/con019575 10 http://www.alzheimers.org.uk/antipsychotics Page 2 of 8
Discontinuing antipsychotics in those aged 65 years and over with BPSD-Table Unless there is severe risk or extreme distress the recommended default management is to discontinue the antipsychotic and monitor/assess using watchful waiting and specific interventions under PAIN or other interventions. If further treatment with antipsychotics is clinically necessary after 12 weeks then a referral to specialist services is advised (DAA, RCGP, DH-Alzheimer s Society : Optimising treatment and care for people with BPSD). Has the patient had antipsychotics for LESS THAN 12 WEEKS? (RCGP,DAA,DH) YES Is the patient on a LOW DOSE? The suggested low doses are*: Risperidone low dose=0.5mg Olanzapine low dose=2.5mg Quetiapine low dose = 50mg Aripiprazole low dose=5mg *These are the suggested doses but it is recommended to check the BNF/SPC. YES NO LOW DOSE Proceed directly with discontinuation and monitoring. Review at 2 weeks. HIGHER DOSE Taper the dose over one month. Reduce to half dose for 2 weeks. GP review at 2 weeks. Discontinue immediately after a further 2 weeks. Review at 2 weeks For patients under review by secondary care then, provided patient is stable, a trial discontinuation of antipsychotic should be recommended alongside management of recurrence of BPSD by the care home (consider nonpharmacological approaches and staff training where necessary). Greater than 12 WEEKS? Establish reason for initiation of antipsychotic and consider whether this is a sound reason for continuing with treatment. Record in notes. See SPC for discontinuation or gradually withdraw treatment by slowly tapering down over at least 3 weeks (Maudsley Guidelines). Closely monitor. Refer to specialist if there are concerns. For patients under review by secondary care, then the same recommendations for a trial discontinuation should apply, but where the patient still requires antipsychotics, the review and responsibility for continued prescribing is to be agreed between primary and secondary care on an individual basis. Page 3 of 8
Tapering of antipsychotic medication: Prior to tapering medication ensure that the patient has no physical health problems associated with BPSD, non-pharmacological approaches of treatment are available and that Care Home staff/carers have had training in management of BPSD. With carer support: Implement small decreases in dose (ensure dose possible with strengths), one step down at a time. Where the antipsychotic is given more than once daily, decrease only one dose to start with, choosing the dose where the patient is likely to be least affected. Allow sufficient time for the patient to adapt to the new dose (usually one to two weeks) before considering the next small reduction in dose. When the lowest dose has been achieved on a daily basis then administer on alternate days before stopping completely. 11 Examples: Drug AM Dose PM Dose Haldol Change to 2 weeks later Aripiprazole Change to 2 weeks later 1mg 1mg 0.5mg 10mg 5mg 2mg 1mg 0.5mg 0.5mg Support material: A leaflet for patients/carer s and a guide for health and social care professionals can be found at //www.alzheimers.org.uk/antipsychotics Quetiapine (Seroquel ) discontinuation in those aged 65 years and over: Quetiapine (Seroquel ) 25 mg, 100 mg, 150 mg, 200 mg, 300 mg film-coated tablets Quetiapine (Seroquel )XL 50 mg, 150mg, 200 mg, 300 mg, 400 mg prolonged-release tablets Switching to Quetiapine (Seroquel ) immediate-release tablets: It is unlikely that a switch from Quetiapine (Seroquel ) XL to Quetiapine (Seroquel ) will be required as multiples of XL 50mg can be used, but this can be done if required by changing the total daily dose taken once daily into divided doses, where the over all total daily does remains the same. The Summaries of Product Characteristics (SPC) states: Elderly patients with dementia-related psychosis Quetiapine (Seroquel ) is not approved for the treatment of patients with dementia-related psychosis. An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical 11 Proposal: Antispychotic Drugs in Dementia- Dr Jill Rasmussen Page 4 of 8
antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Quetiapine (Seroquel ) should be used with caution in patients with risk factors for stroke. In a meta-analysis of atypical antipsychotic drugs, it has been reported that elderly patients with dementia-related psychosis are at an increased risk of death compared to placebo. However in two 10-week placebo-controlled quetiapine (Seroquel ) studies in the same patient population (n=710; mean age: 83 years; range: 56 99 years) the incidence of mortality in quetiapine (Seroquel ) treated patients was 5.5% versus 3.2% in the placebo group. The patients in these trials died of a variety of causes that were consistent with expectations for this population. These data do not establish a causal relationship between Quetiapine (Seroquel ) treatment and death in elderly patients with dementia. For Acute Withdrawal Reactions: Gradual withdrawal over a period of at least one to two weeks is advisable. (This fits in with the advice on gradual withdrawal over at least 3 weeks given by the Maudsley.) http://www.medicines.org.uk/emc/medicine/2295/spc/seroquel+25+mg%2c+100+mg%2c+150+ mg%2c+200+mg%2c+300+mg+film-coated+tablets/ Additional information from SPC Quetiapine treatment is associated with small dose-related decreases in thyroid hormone levels, particularly total T 4 and free T 4. The reduction in total and free T 4 was maximal within the first two to four weeks of quetiapine treatment, with no further reduction during long-term treatment. In nearly all cases, cessation of quetiapine treatment was associated with a reversal of the effects on total and free T4, irrespective of the duration of treatment. Smaller decreases in total T 3 and reverse T 3 were seen only at higher doses. Levels of TBG were unchanged and in general, reciprocal increases in TSH were not observed, with no indication thatquetiapine (Seroquel )causes clinically relevant hypothyroidism. Examples of quetiapine withdrawal: Discontinuing antipsychotic use of up to 12 weeks duration: For patients receiving a low dose antipsychotic (Dementia Action Alliance(DAA),RCGP,DH) 12 : Proceed directly with discontinuation and monitoring. Review at 2 weeks. The suggested low doses are: Quetiapine low dose = 50mg* *These are the suggested doses but it is recommended to check the BNF/SPC. For patients receiving a higher dose antipsychotic (DAA,RCGP, DH) 13 : Taper the dose over one month. Reduce to half dose for 2 weeks. GP review at 2 weeks. Discontinue immediately after a further 2 weeks. 12 http://www.alzheimers.org.uk/antipsychotics 13 http://www.alzheimers.org.uk/antipsychotics Page 5 of 8
Review at 2 weeks GP review Using the above advice from DAA, RCGP & DH gives the following example: Quetiapine (Seroquel ) AM Dose PM Dose Current dose 150mg 150mg Week 1 START DATE 75mg 75mg Week 2 75mg 75mg Week 3 75mg 75mg Week 4 75mg 75mg Week 5 Then review 6 weekly (max 3 monthly) Discontinuation for antipsychotic treatment over 12 weeks duration: Apply general principles SPC advises gradual withdrawal over a period of at least one to two weeks. This is similar to the advice given by the Maudsley (Guidelines 10th edition) on antipsychotic withdrawal which is to gradually withdraw treatment by slowly tapering down over at least 3 weeks. Implement small decreases in dose (ensure dose possible with strengths), one step down at a time. 14 Where the antipsychotic is given more than once daily, decrease only one dose to start with, choosing the dose where the patient is likely to be least affected. Allow sufficient time for the patient to adapt to the new dose (usually one to two weeks) before considering the next small reduction in dose. When the lowest dose has been achieved on a daily basis then administer on alternate days before stopping completely. GP review Examples using the above advice: Immediate release: Quetiapine (Seroquel ) AM dose PM dose Current dose 150mg 150mg Week 1 START DATE 150mg 75mg (3x25mg) Week 2 75mg (3x25mg) 75mg(3x25mg) Week 3 75mg (3x25mg)-consider alternate days for last 3 or 4 days Week 4 Then review 6 weekly (max 3 monthly) 14 Proposal: Antispychotic Drugs in Dementia- Dr Jill Rasmussen Page 6 of 8
The length of time taken for discontinuation can be extended from 3 weeks if required. GP review GP review Quetiapine (Seroquel ) AM dose PM dose Current dose 100mg 100mg Week 1 START DATE 50mg (2x25mg) 100mg Week 2 50mg (2x25mg) 50mg (2x25mg) Week 3 25mg 50mg (2x25mg) Week 4 25mg 25mg Week 5 25mg Week 6 25mg on alternate days Week 7 Then review 6 weekly (max 3 monthly) Modified release: Quetiapine (Seroquel ) XL Current dose Week 1 START DATE Week 2 Week 3 Week 4 Week 5 Then review 6 weekly (max 3 monthly) Daily dose 300mg 200mg (150mg+50mg) 100mg (2x50mg) 50mg 50mg on alternate days Page 7 of 8
Individual Withdrawal Plan (for use when MAR chart not available) Patient Name Date of birth GP Mental Health Contact Current Drug and Dose. Week commencing Morning dose Midday dose Teatime dose Night time dose Observations/ monitoring Comments Week 1: Week 2: Week 3: Week 4: Week 5: Week 6: GP signature.. Date Page 8 of 8