Guidance on the use of mood stabilisers for the treatment of bipolar affective disorder GUIDELINE NO RATIFYING COMMITTEE DRUGS AND THERAPEUTICS GROUP DATE RATIFIED July 2013 DATE AVAILABLE ON INTRANET NEXT REVIEW DATE July 2015 POLICY AUTHORS Jules Haste, Lead Pharmacist, Brighton and Hove Members of the Pharmacy Team (contributors are listed overleaf) . If you require this document in an alternative format, ie easy read, large text, audio, Braille or a community language please contact the pharmacy team on 01243 623349 (Text Relay calls welcome). Page 1 of 52 Contributors Jed Hewitt, Chief Pharmacist - Governance & Professional Practice James Atkinson, Pharmacist Team Leader Mental Health and Community Services Miguel Gomez, Lead Pharmacist, Worthing. Hilary Garforth, Lead Pharmacist, Chichester. Pauline Daw, Lead Pharmacist (CRHTs & AOT), East Sussex. Iftekhar Khan, Lead Pharmacist (S&F Service), East Sussex. Graham Brown, Lead Pharmacist CAMHS & EIS. Gus Fernandez, Specialist Pharmacist MI and MH Lisa Stanton, Specialist Pharmacist Early Intervention Services & Learning Disabilities. Nana Tomova, Specialist Pharmacist, Crawley. Jamie Richardson, Specialist Pharmacist, Crawley. Page 2 of 52 Section Title Page Number 1. Introduction and Key Points 4 2. Flowcharts: Suggested Treatment plans (from BAP guidance) 2.1 Acute mania or mixed episode 6 2.2 Acute depressive phase 7 2.3 Long term or maintenance treatment 8 3. General principles in the treatment of acute mania or mixed 9 episode 4. General principles in the treatment of acute depressive phase 10 5. General principles in long term or maintenance treatment 12 6. Rapid cycling 14 7. Physical health 14 8. Treatment in special situations 8.1 Pregnancy 15 8.2 Breast-feeding 17 8.3 Older adults 19 8.4 Children and adolescents 22 8.5 Learning disabilities 27 8.6 Cardiac dysfunction 29 8.7 Renal dysfunction 31 8.8 Hepatic dysfunction 34 8.9 Epilepsy 38 9. The risk of switching to mania with antidepressants 40 10. Psycho-education 41 11. References 42 Appendix 1 Table of the evidence for bipolar affective disorder treatments 46 Appendix 2 Licensed doses for the mood stabilisers 48 Appendix 3 Side effect profile for the mood stabilisers 49 Appendix 4 Monitoring recommendations for the mood stabilisers. 50 • For antipsychotics and antidepressants please see Trust antipsychotic guidance. • For Lithium prescribing and monitoring please see trust guidance. • Valproate monitoring • Carbamazepine monitoring Page 3 of 52 1. Introduction 1 Bipolar disorder is a cyclical mood disorder involving periods of profound disruption to mood and behaviour interspersed with periods of more or less full recovery. The key feature of bipolar disorder is the experience of hypomania or mania – grandiose and expansive affect associated with increased drive and decreased sleep, which ultimately can culminate in psychosis and exhaustion if left untreated. There is increasing recognition of a spectrum of bipolar disorders that ranges from marked and severe mood disturbance into milder mood variations that become difficult to distinguish from normal mood fluctuation. In terms of classification, in DSM-IV a distinction is drawn between bipolar I disorder, in which the patient suffers full-blown manic episodes (most commonly interspersed with episodes of major depression), and bipolar II disorder, in which the patient experiences depressive episodes and less severe manic symptoms, classed as hypomanic episodes (it must be noted that ICD-10 does not include bipolar II disorder). There is some heterogeneity between the major diagnostic classification systems in the criteria for bipolar disorder. ICD-10 requires two discrete mood episodes, at least one of which must be manic. In DSM-IV a single episode of mania or a single episode of hypomania plus a single major depressive episode would warrant a diagnosis of bipolar disorder. Although mania or hypomania are the defining characteristics of bipolar disorder, throughout the course of the illness depressive symptoms are more common than manic symptoms. The risk of suicide is greatly elevated during depressive episodes. Approximately 17% of patients with bipolar I disorder and 24% of patients with bipolar II disorder attempt suicide during the course of their illness. Annually around 0.4% of patients with bipolar disorder will die by suicide, which is vastly greater than the international population average of 0.017%. The standardised mortality ratio (SMR) for suicide in bipolar disorder is estimated to be 15 for men and 22.4 for women. Community-based epidemiological studies consistently report the lifetime prevalence of bipolar I disorder to be approximately 1% and bipolar II disorder at 0.2-5.0%. The prevalence of bipolar I disorder is similar in both men and women. Comorbid anxiety disorders and substance abuse are reported in 30-50% of patients with bipolar disorder. Bipolar disorder has a fairly early age of onset, with the first episode usually occurring before the age of 30. The peak in onset rate occurs between the ages of 15 and 19 years. Treatment and care should take into account people’s individual needs and preferences. People with bipolar disorder should have the opportunity to make informed decisions about their care and treatment. Good communication between healthcare professionals and patients is essential. When talking to people with bipolar disorder and their carers, healthcare professionals should use everyday, jargon-free language to give a full and clear explanation of bipolar disorder and its treatment. Written, evidence-based information about the condition and its treatment should also be Page 4 of 52 provided. All information should be tailored to the needs of the individual patient. The treatment, care and information provided should be culturally appropriate and in a form that is accessible to people who have additional needs, such as people with physical, cognitive or sensory disabilities, and people who do not speak or read English. Unless specifically excluded by the patient, carers and relatives should have the opportunity to be involved in decisions about the patient’s care and treatment. Carers and relatives should also be provided with the information and support they need. Information leaflets on medication approved by the trust can be found on the following link. http://www.sussexpartnership.nhs.uk/service-users/what-happens/medication 1.2 Key points from the guidance • Treatment selection should be guided where possible, by patient preference. • Valproate should not be prescribed routinely for women of child-bearing potential. If no effective alternative to valproate can be identified, adequate contraception should be used, and the risks of taking valproate during pregnancy should be explained. • A second generation (atypical) antipsychotic should be considered because of its generally more favourable short-term adverse effect profile, especially in relation to motor side effects and the evidence of efficacy that drugs in this class have as anti-manic agents. • Lithium prescribing and monitoring must follow Trust guidance due to a NPSA alert. 4 The latest trust guidelines for the prescribing and monitoring of lithium therapy can be found on the following link http://www.sussexpartnership.nhs.uk/gps/med-info/med- docs/finish/2030/5137 • Lithium may not be appropriate if compliance is poor. • Carbamazepine (CBZ) interacts with many other medications and this should be taken into consideration when prescribing (see appendix 4). • Antidepressants should be tapered and discontinued in mania. Page 5 of 52 Flowchart 1 – Manic/Mixed episode (Flow chart adapted from BAP Guidelines 2009 (2) ) Bipolar Disorder Manic / Mixed episode Assessment: Safety, patient and family preferences and consider need for admission Explain treatment plan including need for medicines Severe Mild Rx IM antipsychotic Rx oral Rx oral antipsychotic or or benzodiazepine if antipsychotic or valproate or lithium (or required valproate carbamazepine) On antidepressants: Taper and discontinue Sleep deprived: Consider short term benzodiazepines Already on long term Rx: Optimize and continue Poor response Review Good response Combination Rx or ECT response Consider maintenance Rx Page 6 of 52 Flowchart 2 – Depressive episode (Flow chart adapted from BAP Guidelines 2009 (2) ) Bipolar Disorder Depressive episode Assessment: Suicide risk, patient and family preferences and treatment setting Severity of risks, treatment options, eliminate stressors Mild and/or previous Severe Moderate mood instability Quetiapine or lamotrigine, Quetiapine or Consider ECT SSRI or other AD (not TCA) lamotrigine NO Add anti-manic agent if BP1 Consider psychological therapies Page 7 of 52 Flowchart 3 - Acute episode resolved (Flow chart adapted from BAP Guidelines 2009 (2) ) Acute episode resolved (euthymia) Bipolar Disorder Ensure education, information and adherence Consider maintenance therapy If mania predominates If depression predominates Protect against manic pole Protect against depression pole Consider lithium, Consider quetiapine or aripiprazole, quetiapine, lamotrigine valproate or olanzapine 2nd Line 2nd Line Carbamazepine Lithium Rx failure / Rx failure / rapid cycling rapid cycling Combination therapy Relapse prevention strategies, CBT Outpatient supervision by specialist clinician Page 8 of 52 2. General principles in the treatment of acute mania or mixed episode. 1, 2 2.1 For patients not on long-term treatment for bipolar disorder a. For severe manic or mixed episodes,