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CLINICAL OVERVIEW OF LITHIUM

CLINICAL OVERVIEW OF LITHIUM. Dr Rana Fahmy Specialist Registrar Wandsworth Early Intervention in Psychosis Service. When should lithium be used? Mechanism of action Clinical use of lithium Lithium monitoring NPSA alert and launch of the patient lithium pack. Overview. Overview.

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CLINICAL OVERVIEW OF LITHIUM

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  1. CLINICAL OVERVIEW OF LITHIUM Dr Rana Fahmy Specialist Registrar Wandsworth Early Intervention in Psychosis Service

  2. When should lithium be used? Mechanism of action Clinical use of lithium Lithium monitoring NPSA alert and launch of the patient lithium pack Overview

  3. Overview • When should lithium be used? • Bipolar disorder • Mania • (bipolar depression) • Prophylaxis • Unipolar depression • Treatment refractory depression

  4. Bipolar Mania

  5. Treatment of acute mania:lithium or divalproex versus placebo 30 Placebo Mania rating scale Lithium Divalproex 14 7 14 21 Days Bowden et al., JAMA 1994

  6. Effectiveness of lithiumPrevious Manic Episodes and Response Placebo Lithium Divalproex 10 8 6 Manic syndrome score improvement 4 2 0 0 2 4 6 8 10 12 14 16 18 Previous manic episodes Swann et al, 2000

  7. 30 65 75 70 35 25 Effectiveness of lithium in acute mania 100 90 80 70 60 50 40 30 20 10 0 With ‘classic’ mania . With mixed mania With rapid cycling Lithium responders Lithium non-responders Adapted from: Calabrese, Bowden & Woyshville (1995)

  8. Acute Mania: NICE guidelines • Stop antidepressant (if taking) either abruptly or gradually • Atypical antipsychotic (olanzapine, risperidone, quetiapine) for those with severe mania • If ineffective consider adding Li or valproate • Valproate or Li if previous good response and compliance • Avoid valproate in women of child bearing potential • Li only if less severe

  9. Bipolar Depression

  10. Lithium in acute BP Depression: An 8 week, DB monotherapy study vs PLC • n= 267 • Lithium did not separate from PLC for any outcome + + p< 0.123 vs PLC Young et al, presented at ISBD 2008, Delhi, Januar26-30

  11. Bipolar depression • Guidelines (e.g. NICE, BAP) unclear due to current lack of evidence • Suggestion that antidepressants of limited utility • Most guidelines recommend optimisation of mood stabilisers (e.g. lithium) • Evidence re lithium • Probably ineffective as monotherapy • May be useful in combination (e.g. with lamotrigine) • May decrease suicidality independently

  12. Bipolar Prophylaxis

  13. Lithium v placebo, maintenance in bipolar disorder

  14. Bipolar prophylaxis: NICE guidelines • First line: lithium, olanzapine or valproate • If fails monotherapy over 6 months • Li + valp, Li + olanz, Valp + olanz • If combination fails • Consider lamotrigine (esp. BPII), carbamazepine, referral to tertiary centre

  15. Unipolar depression: Treatment refractory depression

  16. Lithium augmentation in TRD: placebo controlled studies Response 40% 17% Crossley & Bauer 2007

  17. Treatment refractory depression: BAP guidelines consider adding lithium (A), olanzapine (A), quetiapine (B), risperidone (B), aripiprazole (B), tri-iodothyronine (B) or mirtazapine (B) Be aware that the evidence mainly supports Li and T3 added to TCAs and the other drugs added to SSRIs

  18. Overview • When should lithium be used? • Mechanism of action • Clinical use of lithium

  19. Overview • When should lithium be used? • Mechanism of action • Clinical use of lithium • Stopping/starting • Side effects & toxicity • Use in pregnancy

  20. Effects of Rapid discontinuation of Li in BP-I Patients From Suppes et al, 1991. 100 Gradual (N=15) 80 60 Percent remaining in remission 40 20 Rapid (N=108) 0 0 10 20 30 40 Time after stopping Lithium (months)

  21. 6 months stable on Li 27 months stable on Li No Li Lithium Minimum 27 months treatment for benefit 50% relapse brought forward 21 months Effect of lithium withdrawal on long term usage 120 100 80 60 40 20 0 0 3 6 9 12 15 18 21 24 27 30 Time (months) Goodwin (1994) B.J.Psych.

  22. Lithium Discontinuation: Suicide Risk N = 310 310 185 133

  23. Lithium Pharmacokinetics • Carbonate or citrate salts • rapid absorption in upper GIT • peak levels after 2-3 hours • total absorption may take 8 hours • Preparations have differing bioavailability • Narrow therapeutic index • Renal excretion at a constant rate proportional to GFR • Steady state after 5-7 days • Levels obtained at 12 hours • Levels increased by NSAIDs, diuretics, ACE inhibiters

  24. Lithium Drug Interactions

  25. Lithium dose in maintenance • Multicentre study of patients with bipolar disorder randomised to low lithium levels (0.4 to 0.6 nmol/l) or higher levels (0.8 to 1.0) • higher rates of adverse effects and poorer compliance in high levels group • 2.6 fold higher rate of relapse with low lithium levels • but highest risk of relapse was in those whose lithium levels were reduced Gelenberg et al 1989; Rosenbaum et al 1992

  26. Adverse effects of lithium • Occur in 75% of patients • thirst, polydipsia, polyuria • weight gain and tremor • precipitates or worsens skin problems • mild impairment of attention and memory • T wave flattening/inversion in 30% patients • GI disturbance • leucocytosis

  27. Adverse effects of lithium (cont) • hypothyroidism and non-toxic goitre [5%] • may lead to depression and/or rapid-cycling • impaired renal tubular function [5-10%] • impaired glomerular function [possible]

  28. Lithium toxicity • usually inadvertent • signs appear at levels above 1.3 mmol/l • early • worsened side effects, nausea and vomiting, marked tremor, blurred vision, vertigo, confusion, hyperreflexia • late • disorientation, dysrythmia, convulsions, coma • death results from cardiac effects or pulmonary complications • can occur at therapeutic levels • EEG changes can be diagnostic

  29. Use in pregnancy and lactation • Major congenital anomalies in early pregnancy • 4-12 % of births (cf 2-4% in untreated comparison groups) • Cardiovascular anomalies in 0.05-1% • includes Ebsteins anomaly [downward displacement of tricuspid valve, arrhythmia, heart failure] • Ebsteins is rare • 1 in 2000 with Lithium (estimate) • 1 in 20 000 in general population • Use contraindicated in breast feeding • Li excreted in breast milk

  30. Lithium Monitoring

  31. POMH UK • Prescribing observatory for mental health UK • National case note audit of lithium monitoring (Topic 7) (n= ~3000) • Renal function, thyroid function, lithium levels and weight/BMI/waist circumference • Used NICE standards • 1 in 10 had no lithium level documented. 70% did not meet NICE standard for lithium levels • Issues of documentation, shared care, access to pathology results

  32. Actions: • 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. Thislevel of monitoring is required as clinically observable side effects may not be apparent even with toxic levels

  33. Actions: 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

  34. Actions: 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 and the NPA have developed support material for this action

  35. Actions: 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.

  36. Actions: 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

  37. http://www.nrls.npsa.nhs.uk/alerts/?entryid45=65426

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