1. Bipolar Disorder and Lithium Prescribing Dr Stuart Adams Consultant Psychiatrist Cheam CMHT

2. Q1: Indicate whether the following statements are True or False:- Valproate should never be prescribed in women of child bearing age (T/F) Bipolar disorder has a prevalence rate of 1% (T/F) Lithium reduces the risk of suicidal behaviour in patients with bipolar disorder (T/F) Antidepressants should always be discontinued in patients presenting with mania (T/F)

3. Q2: The following are side effects of lithium treatment:- 1.Blurred vision (T/F) 2.Hypothyroidism and hyperparathyroidism (T/F) 3.Increased Gastrointestinal disturbances (T/F) (anorexia, vomiting, diarrhoea) 4.Muscle weakness (T/F) 5.Polyuria, polydypsia (T/F) 6.Fine Tremor (T/F)

4. Q3: Which of the drugs listed below have potential risk of causing lithium toxicity if given with Lithium:- 1.Carbamazepine (T/F) 2.SSRI (T/F) 3.ACE inhibitors (T/F) 4.Antipsychotics (T/F) 5.Antacids without sodium bicarbonate (T/F)

5. Bipolar disorder is complex… Bipolar disorder is an episodic, potentially life-long, disabling disorder that can be difficult to diagnose Need to improve recognition, reduce sub- optimal care and improve long-term outcomes There is variation in management of care across healthcare settings

6. How to diagnose….. Bipolar disorder is a cyclical mood disorder Abnormally elevated mood or irritability alternates with depressed mood – bipolar I – at least one manic or mixed episode – bipolar II – at least one major depressive episode and at least one hypomanic episode

7. PresentationKey features ManiaElevated, expansive or irritable mood With or without psychotic symptoms Marked impairment in functioning HypomaniaElevated, expansive or irritable mood No psychotic symptoms Less impairment of functioning DepressionMild, moderate or severe With or without psychotic symptoms Rapid cyclingAt least four episodes in 1 year Mixed statesManic and depressive features present during same episode

8. Incidence and prevalence….. Annual incidence – 7 per 100,000 Estimated lifetime prevalence – bipolar I – 4–16 per 1000 Peak onset between 15 and 19 years of age Suicide – bipolar I – 17% attempt suicide – bipolar disorder – 0.4% die annually by suicide

9. Co-morbidity is common….. Anxiety – 30–50% Substance misuse disorders (drugs and alcohol) – 30–50% Personality disorders, in particular borderline personality disorder (exercise caution when diagnosing)

10. Primary care management…. Refer to confirm diagnosis….. – Consider EIT referral Pharmacological management – Treat the acute phase Monitor….

11. Treat the acute phase….. Consider an antipsychotic if: – manic symptoms are severe – there is marked behavioural disturbance Consider valproate or lithium if: – there has been previous response and good compliance with one of these drugs Consider lithium if: – symptoms are less severe

12. Initiate long-term pharmacological treatment… After a manic episode with significant risk and adverse consequences Bipolar I: two or more acute episodes Bipolar II: evidence of significant functional impairment or risk of suicide or frequently recurring episodes

13. Choose long-term drugs….. Base choice of lithium, olanzapine or valproate* on: – previous response – risk and precipitants of manic versus depressive relapse – physical risk factors – patient preference and history of adherence – cognitive state assessment if appropriate * Valproate should not be prescribed routinely for women of child-bearing potential

14. Support long-term pharmacological treatment… Ensure prescribing advisers are aware of NICE guidance, and what to consider when choosing treatment Focus on optimising appropriate long-term treatment Support service user education and empowerment in pharmacological treatment and management decisions Make use of early intervention teams, regional mental health trusts and CAMHS teams

15. Use antidepressants with care…. Acute manic phase Stop antidepressants at onset of acute manic phase and decide if discontinuation is abrupt or gradual based on: – current clinical need – previous experience of discontinuation/withdrawal symptoms – the risk of discontinuation/withdrawal symptoms

16. Consider need for treatment… Is long-term antidepressant treatment needed after an acute depressive episode? No evidence for reduced relapse rates May be associated with increased risk of mania

17. Consider psychological therapy… For those who are stable, individual structured psychological therapy should include: – at least 16 sessions over 6 to 9 months – psychoeducation – promotion of medication adherence – monitoring of mood, detection of early warnings and prevention strategies – coping strategies

18. Take possible pregnancy into account Valproate should not be used routinely for women who may become pregnant. It may: – cause foetal abnormalities – affect the child’s cognitive development If prescribed, ensure adequate contraception. Explain risks during pregnancy and to the health of the unborn child An antipsychotic may be used with caution

19. Mitigate drug-related weight gain Review medication strategy and consider: – dietary advice and support – advising regular increased aerobic exercise – referring to a specialist mental health diet clinic or health delivery group – referring to a dietitian if needed for people with complex co-morbidities

20. Review annually Over the course of the year an annual review should include: lipid levels, including cholesterol, in patients over 40 plasma glucose levels weight smoking status and alcohol use blood pressure

21. Patient Safety Alert “Safer Lithium Therapy”

22. Indications for using Lithium: 1.Bipolar Affective disorder Type 1 2.Treatment of Unipolar Depression 3.Reducing suicidal risk and suicidal behaviour 4.Other licensed uses include treatment of aggressive or self-mutilating behaviour. 5.Unlicensed uses include the prevention and treatment of steroid induced psychosis the elevation of the white blood cell count in patients prescribed clozapine.

23. Actions: 1.Patients prescribed lithium are monitored in accordance with NICE guidance NICE specifies lithium blood levels are used to adjust dosage at least every 3 months and that thyroid function tests and renal function tests are undertaken every 6 months. This level of monitoring is required as clinically observable side effects may not be apparent even with toxic levels

24. Actions: 2.There are systems in place to ensure that the results of blood tests are communicated between laboratories and prescribers. Whether in primary or acute setting, levels must be available when dosing decisions are taken

25. Actions: 3.At the start of lithium therapy and throughout their treatment patients receive appropriate ongoing verbal and written information and a record book to track lithium blood levels and relevant clinical tests. The NPSA with POMH-UK have developed support material for this action

26. Side effects: Fine Tremor Gastrointestinal disturbances Polyuria, polydypsia Weight gain & oedema Hair loss, Acne, Psoriasis: precipitated and exacerbated Hypothyroidism, hyperparathyroidism Hyperglycaemia, hypocalcaemia, hypomagnesaemia

27. Toxic effects: ( Most patients experience toxic effects with levels above 1.5mmol/L) Blurred vision Increased Gastrointestinal disturbances (anorexia, vomiting, diarrhoea) Muscle weakness CNS disturbances (drowsiness, lethargy, ataxia, coarse tremor, impaired co-ordination, dysarthia)

28. Actions: 4.Prescribers and pharmacists check that blood test are being monitored regularly and that test results are safe before issuing or dispensing repeat prescriptions. Standard Operating Procedures (SOPs) will describe clear processes for both prescribing and dispensing that must be adhered to if monitoring falls below safe standards or patient are unwilling to share information.

29. Actions: 5.Systems are in place to identify and deal with medicines that might adversely interact with lithium therapy. SOPs, decision support systems, patient medication records, patient records, inpatient charts, medication administration records reflect the need to identify and deal with potential interacting medicines whether on prescription or brought over-the-counter

30. Common Drugs that Lithium shows Interaction with are: 1. Analgesics: Excretion of Lithium is reduced by NSAIDS e.g. Ibuprofen, Diclofenac, Indomethacin 2. ACE inhibitors by reducing Glomerular perfusion pressure increases re absorption of lithium and hence, toxicity. 3. Diuretics e.g. Frusemide: increased toxicity with medications that cause sodium depletion.

31. Common Drugs that Lithium shows Interaction with are: 4. Anti-epileptics: Neurotoxic effect with Carbamazepine 5. Anti Psychotics: Neurotoxic and increased risk of extra pyramidal side effects but can be used with caution 6. Anti Depressants: increase lithium toxicity with SSRI’s, Venlafaxine, and Tricyclics. 7. Antacids: excretion of lithium is increased by sodium bicarbonate

32. The Lithium Booklet 24 page booklet with: – details of the patient – supporting health provider services – current drug therapy Provides information each patient must know and understand in order to make lithium therapy safe.

33. The Lithium Alert Card Credit card size Carried by the patient at all times. Informs healthcare professionals that the patient is taking a specific brand of lithium and provides details of contacts in an emergency.

34. The Lithium Record Book

35. Q1: Indicate whether the following statements are True or False:- Valproate should never be prescribed in women of child bearing age FALSE Bipolar disorder has a prevalence rate of 1%TRUE Lithium reduces the risk of suicidal behaviour in patients with bipolar disorder TRUE Antidepressants should always be discontinued in patients presenting with mania TRUE

36. Q2: The following are side effects of lithium treatment:- 1.Blurred vision FALSE (toxicity) 2.Hypothyroidism and hyperparathyroidism TRUE 3.Increased Gastrointestinal disturbances FALSE (toxicity) 4.Muscle weakness FALSE (toxicity) 5.Polyuria, polydypsia TRUE 6.Fine Tremor TRUE

37. Q3: Which of the drugs listed below have potential risk of causing lithium toxicity if given with Lithium:- 1.Carbamazepine TRUE 2.SSRI TRUE 3.ACE inhibitors TRUE 4.Antipsychotics TRUE 5.Antacids without sodium bicarbonate FALSE

38. References…. Quick reference guide – a summary www.nice.org.uk/CG038quickrefguide NPSA lithium Alert http://www.nrls.npsa.nhs.uk/resources/?entry id45=65426