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Public Health Wales Lithium Monitoring Lithium Monitoring Quality improvement toolkit - Appendices Author: Primary Care Quality and Information Service Date: February 2012 Version: 1 Status: Final Intended audience: Public (Internet) / NHS Wales (Intranet) / Public Health Wales (Intranet) Purpose and summary of document: This document is for use by general practices to ensure that the delivery of service to people prescribed Long Term Lithium therapy is evidence based and in line with best practice. The audit toolkit will provide the user with a summary of the current evidence directing the safe provision of service. The toolkit will support practices to review and improve where necessary by providing information about the care of patients on Lithium therapy and also suggests appropriate READ codes that the practice is likely to use. Also included is an evaluation sheet to feedback on the information provided Publication / distribution: Publication in Public Health Wales Document Database (Primary Care Quality and Information Service) Link from Public Health Wales e-Bulletin Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 1 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Contents Appendix Page A Lithium Monitoring 3-12 B Lithium Shared Care Protocol 13-22 C Further Information 23 -24 D READ Codes 25-26 E Evaluation Sheet 27 F References 28 © 2012 Public Health Wales Material contained in this document may be reproduced without prior permission provided it is done so accurately and is not used in a misleading context. Acknowledgement to the Public Health Wales to be stated. Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 2 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Appendix A – Lithium Monitoring Lithium Monitoring 1,2,3,4,5,67,8,9,10,11,12 Initial Commencement – Lithium should not be initiated routinely in primary care for the treatment of bipolar disorder 2 General medical history, physical examination, Full blood count, BP height and weight 1,2,5,9 Advise patients that erratic compliance and discontinuation may increase risk of relape 2 Estimated glomerular filtration rates, thyroid function 1,6, U&E and serum creatinine 2,6 ECG for patients with cardiovascular disease 2,5,6,9 Serum electrolyte levels including serum calcium 6 Full blood count if clinically indicated 2 Shared care protocol with the patient’s GP for prescribing and monitoring lithium and checking adverse effects 2,3,5 Pregnancy test (women of childbearing age) 1,2 Discus common side effects and toxicity 6 Discuss dose change and the need for continued therapy 6 Discuss adequate fluid intake 12 Aware that patients should take lithium for at least 6 months to establish its effectiveness as a long-term treatment 2 Prescribing: Lithium is always prescribed by brand name 5,9 Lithium is available as two salts: (i) Lithium Carbonate supplied in tablet form (Camcolit, Liskonum, Priadel). (ii) Lithium Citrate supplied as a liquid (Priadel and Li-Liquid). 5,9,10 5,9,10 Lithium should be considered for the long-term treatment of bipolar disorder 2 acute mania or hypomanic episodes, 6 recurrent depressive disorder, 6 control of aggressive behaviour or intentional self harm 6 Serum lithium levels should be checked 1 week after starting and 1 week after every dose change, and until the levels are stable 2 Ensure lithium serum levels are in therapeutic range 0.5 -1.0 mmol/l 1 Lithium is usually best given as a single dose at night. 1 All blood samples taken for monitoring of lithium levels should be done approximately 12-16 hours following the last dose of drug. 2 This is important and failure to do so may result in misleading results and consequently ill informed clinical action. 6 Lithium is the treatment of choice for relapse prevention for bipolar affective illness. Lithium should be prescribed at an appropriate dose with a daily dosing regimen. 3 3 The highest dose that produces minimal side effects should be employed. Levels less than 0.5mmol/l are usually too low. 1 Lithium may be effective in a minority of patients as a monotherapy. 1 Author: Primary Care Quality and Date: February Status; Final Information Service 2012 Intended Audience; Public Lithium Monitoring; Version 1 3 (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring A serum lithium level of 0.6–0.8 mmol/L is suitable for people who are being prescribed lithium for the first time. 2,9 Higher serum lithium levels (0.8 – 1.0 mmol/l are suitable for people who have relapsed previously while taking lithium or who still have sub-threshold symptoms with functional impairment while receiving lithium a trial of at least 6 months with serum lithium levels between 0.8 – 1.0 mmol per litre should be considered. 2,9 Titrate dosage further upward if necessary (generally to serum concentrations of 0.5 – 1.0 mmol/l) according to response and side effects. 1 Check lithium level after later dosage increases (steady levels are likely to be reached approximately 5 days after dosage adjustment). 1 The ‘optimal’ maintenance level is the highest dose tolerated without significant side effects. It will vary from patient to patient. 1 Older patients, and others with reduced renal function, will require lower doses of lithium 1 As a group they are more prone to side effects due to increased end organ sensitivity, reduced circulation and reduced renal clearance. 1 In acute mania, higher serum levels (1.0 – 1.2 mmol/l) are claimed to be more efficacious, but vigilance is required for adverse effects. 1 The National Patient Safety Agency (NPSA) has asked all healthcare organisations in the NHS where lithium therapy is initiated , prescribed, dispensed and monitored to ensure that by 31 December 2010: 4 Patients prescribed lithium are monitored in accordance with NICE guidance There are reliable systems to ensure blood test results are communicated between laboratories and prescribers 4 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 4 4 The NPSA has developed a patient information booklet, lithium alert card and record book for tracking blood tests. 4 Copies are available: mailto:[email protected] Prescribers and pharmacists check that blood tests are monitored regularly and that it is safe to issue a repeat prescription and / or dispense the prescribed lithium. 4 Systems are in place to identify and deal with medicines that might adversely interact with lithium therapy. 4 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 4 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Monitoring lithium For patients on long term lithium treatment prescribers should monitor the following:2,5,6,8,9,11 Monitor serum levels normally every 3 months 2,5,6,8,11 Monitor older adults carefully for symptoms of lithium toxicity because they may develop high serum levels of lithium at doses in the normal range and lithium toxicity is possible at moderate serum lithium levels 2 Monitor weight, especially in patients with rapid weight gain 2,9 Undertake more frequent tests if there is evidence of clinical deterioration, abnormal results, a change in sodium intake, or symptoms suggesting abnormal renal or thyroid function such as unexplained fatigue, or other risk factors, for example, if the patient is starting medication such as ACE inhibitors, nonsteroidal anti-inflammatory drugs, or diuretics 2 Arrange thyroid and renal function tests every 6 months, and more often if there is evidence of impaired renal function 2,6,11 Initiate closer monitoring of lithium dose, and blood serum levels if urea and creatinine levels become elevated, and assess the rate of deterioration of renal function. 2 Monitor renal function six monthly by checking urea and electrolyte levels and eGFR 6 The decision whether to continue lithium depends on clinical efficacy, and degree of renal impairment: prescribers should consider seeking advice from a renal specialist and a clinician with expertise in the management of bipolar disorder on this 2 Serum calcium annually 5,6 Full blood count annually and as clinically required 2 Consider ECG monitoring for patients at high risk of cardiovascular disease 2,11 Monitor for symptoms of neurotoxicity, including paraesthesia, ataxia, tremor and cognitive impairment, which can occur at therapeutic levels 2 Monitoring of laboratory values Lithium levels are normally measured 1 week after starting therapy, 1 week after every dose change and weekly thereafter until the levels are stable. The aim should be to maintain serum lithium levels between 0.6 and 0.8 mmol/l in patients being prescribed lithium for the first time. 2 Lithium blood levels should be measured 12 hours post-dose 4,9 Baseline renal function tests, thyroid function tests, and a full blood count are normally measured at the start of treatment. Thereafter thyroid and renal function tests should be monitored every 6 months (or more often if there is evidence of impaired renal function). 2,9 Initiate closer monitoring of lithium dose and blood serum levels if urea and creatinine levels become elevated, and assess the rate of deterioration of renal function. 2 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 5 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Undertake more frequent tests if there is evidence of clinical deterioration, abnormal results, a change in sodium intake, or symptoms suggesting abnormal renal or thyroid function. 2 Renal and thyroid function should be checked every 12 months in stable patients or whenever the clinical status changes. 1 Compliance Lithium discontinuation by patients is extremely common and is associated with admission to hospital. This association will be due in large part to manic relapse which is provoked by abrupt lithium discontinuation. Unless patients are adherent to lithium for a minimum of 2 years, these withdrawal effects will nullify any potential prophylactic effect. 1 Pregnancy Lithium should not routinely be prescribed for pregnant women with bi-polar disease because of risk of harm to the fetus, such as cardiac problems. 2,6 Women of childbearing age should use reliable contraception. Lithium is contraindicated in the 1st trimester of pregnancy and breast feeding. If the pregnancy is confirmed in the 1st trimester, and the woman is stable, lithium should be stopped gradually over 4 weeks, and the woman informed that this may not remove the risk of cardiac defects in the fetus. 2 Women with bi-polar disease considering pregnancy should normally be advised to stop lithium therapy and an alternative considered. 2 Women with severe bipolar disorder, who are maintained on lithium, can be continued on lithium during pregnancy if clinically indicated. 3 Options to consider for women taking lithium and considering pregnancy: 2 If the patient is well and not at high risk of relapse gradually stopping lithium. If the patient is unwell or at high risk of relapse: Switching gradually to alternative or Stopping lithium and starting in second trimester if not planning to breastfeed. Continuing with lithium and discussing risks. If the woman decides to stay on lithium during pregnancy: 2,6 Serum lithium levels should be monitored every 4 weeks Weekly from 36th week 24hrs after childbirth Dose adjusted to keep serum levels within therapeutic range Maintain adequate fluid levels The newborn should have a full paediatric assessment with social and medical help. 2 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 6 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Women should be advised not to breastfeed if taking lithium 2,3,6 This is particularly if the infant is not full-term and healthy. If a decision is made to proceed, close monitoring of the infant, including serum lithium levels, should be undertaken. 3 Relapse Relapse rates on lithium over a year or so were 40% compared with about 60% on placebo. That means, in general, one would need to treat about four patients for a year with lithium to avoid one relapse. There are fewer relapses at times beyond a year: the patients who do well on Lithium continue to do well on it. 1 Abrupt discontinuation increases the risk of relapse. 10 For people who have relapsed previously while taking lithium or who still have subthreshold symptoms with functional impairment while receiving lithium, a trial of at least 6 months with serum lithium levels between 0.8 and 1.0 mmol per litre should be considered. 2 Lithium mono-therapy is probably effective against both manic and depressive relapse, although it is more effective in preventing mania 1 Erratic compliance or rapid discontinuation may increase risk of manic relapse. Overdose 2 7 If an acute overdose has been taken by a patient on chronic lithium therapy, this can lead to serious toxicity occurring even after a modest overdose as the extravascular tissues are already saturated with lithium. Lithium toxicity can also occur in chronic accumulation for the following reasons: 7 Acute or chronic overdosage. Dehydration e.g. due to intercurrent illness. Deteriorating renal function. Drug interactions, most commonly involving a thiazide diuretic or a non-steroidal anti-inflammatory drug (NSAID). In patients with a raised lithium concentration, the risk of toxicity is greater in those with the following underlying medical conditions: hypertension; diabetes; congestive heart failure; chronic renal failure; schizophrenia; Addison's disease. 7 Most patients experience toxic effects with levels above 1.5 mEq/L; levels above 2.0 mEq/L are associated with life-threatening side effects and require urgent treatment: haemodialysis may be needed to minimize toxicity. 1,10 Lithium toxicity should also be suspected at ‘therapeutic’ levels in compromised patients with relevant symptoms. 1 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 7 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Contraindications Cardiac disease 9 Renal impairment 9 Untreated hypothyroidism 9 1st Timester of pregnancy 9 Breastfeeding 9,12 Low body sodium levels, patients on low sodium diets and those who are dehydrated 9 Addison’s disease 9 Side effects Side effects include tremor, polyuria, polydipsia, hypothyroidism, 3,4 weight gain, cognitive problems, sedation or lethargy, impaired co-ordination, gastrointestinal distress 3,4,10, hair loss, benign leukocytosis, acne and oedema Lithium can precipitate and exacerbate psoriasis 1 The common side effects can usually be reduced or eliminated by lowering the lithium dose or changing the dosage schedule. 1 With long term lithium treatment (>10 years), 10% - 20% of patients display morphological kidney changes. These changes are not generally associated with renal failure, although there are case reports of renal insufficiency attributed to lithium. 1 Drug Interactions (Refer to interaction section of BNF) 10 There must be effective communication between all healthcare practitioners involved with patients on lithium therapy. This will ensure the impact of interacting medicines is considered when clinical decisions are made. 4 While many medications have been reported as interacting with lithium monitoring must highlight as a minimum the potential for lithium’s interactions with the following commonly prescribed therapies and OTC medicines: 4,6 1. thiazides and related diuretic; 2. ACE inhibitors 3. non-steroidal anti-inflammatory drugs (NSAIDS); 4. sodium bicarbonate containing, non-prescription antacids or urinary alkalinising agents 4 Concomitant use may cause lithium toxicity or with sodium containing antacids subtherapeutic levels. 4 Diuretics Thiazide diuretics can increase serum lithium levels by reducing clearance of lithium. People who are stabilized on lithium and begin taking thiazide diuretics are at significant risk of developing lithium toxicity. Toxic lithium concentrations may be seen within 3 –5 days. Loop diuretics also cause lithium retention but are less likely to result in lithium toxicity 9,12 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 8 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Ace Inhibitors Decrease the excretion of lithium. They can also precipitate renal failure. If these two drugs are prescribed together, extra care is required in monitoring both serum creatinine and lithium 9 Non steroidal anti-inflammatory drugs (NSAIDs) Patients taking lithium should be warned not to take over-the-counter NSAIDs. Prescribing NSAIDs for such patients should be avoided if possible, and if they are prescribed the patient should be closely monitored.2 Reduce lithium excretion – avoid if possible 12 May increase serum lithium levels by up to 40%. The mechanism of this interaction is thought to be related to the effects of NSAIDs on fluid balance. This is particularly important if NSAIDs are added to a long-standing prescription of lithium. 9 Haloperidol Although severe neurotoxicity has been reported with this combination, if lithium levels are maintained in the therapeutic range (0.6–1.0 mmol/L) and the haloperidol dose is not increased rapidly above the recommended maximum, the chance of inducing a toxic state is very low 9 Carbamazepine In combination with lithium has been reported to cause neurotoxic reactions. Higher (greater than 1 mmol/L) plasma lithium levels were involved than are now thought acceptable, so a neurotoxic reaction to lithium alone was a risk factor. Carbamazepine and lithium may therefore be usefully co-prescribed 9 Antidepressants With a serotonergic action (such as selective serotonin reuptake inhibitors, tricyclic antidepressants, venlafaxine, duloxetine) have rarely been linked to an increased incidence of central nervous system toxicity when used with lithium. The mechanism of this interaction is not well understood. Prescribers should check lithium levels soon after starting treatment with a serotonergic antidepressant, although there are some reports of neurotoxic reactions in the absence of raised lithium levels 9,12 Signs / Symptoms and Management of Toxicity Most patients experience toxic effects with levels above1.5 mmol/l; 6,9,12 Levels above 2.0mmol/l are associated with life-threatening side effects and require urgent treatment: haemodialysis may be needed to minimise toxicity. 6,9 Lithium toxicity should also be suspected at ‘therapeutic’ levels in compromised patients with relevant symptoms 9 Signs / Symptoms Management 10 Nausea & vomiting Anorexia, diarrhoea 12 Blurred Vision6 Coarse tremor10 Muscle weakness10 Lack of co-ordination10 Lithium toxicity is a medical emergency, 9,10 because it can result in permanent neurological damage and death. It is treated by the withdrawal of lithium treatment, fluid replacement and sometimes haemodialysis. 9 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 9 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Mild drowsiness 6 Sluggishness 10 Progressive giddiness10 Ataxia 6 Dysarthia 12 Levels above 2.0mmol/l Hyperreflexia, hyperextension of the limbs, toxic psychoses, convulsions, syncope, oliguria, circulatory failure, coma and death 6,9,10,12 Levels are monitored every 6-12 hours 9 The risk of toxicity is greater in people with hypertension, diabetes, congestive heart failure, chronic renal failure, schizophrenia or Addison’s disease. 9 Guidance to Patients Patients taking lithium should be advised to: Carry a lithium card Regular blood tests are important and the results should be recorded in their lithium record booklet Adverse effects to expect. Monitor weight if rapid weight gain How to recognize the symptoms of lithium toxicity Not to take over the counter Non-steroidal anti inflammatory drugs Seek medical attention if they develop diarrhoea and/or vomiting or any form of dehydration, will lead to sodium depletion and therefore increase plasma lithium levels 2 Ensure they maintain their fluid intake, particularly after sweating (for example, after exercise, in hot climates, or if they have a fever), if they are immobile for long periods or—in the case of older people—develop a chest infection or pneumonia 2 If a dose is missed they should take it as soon as possible; but should not double the dose Do not stop taking lithium abruptly, and that non compliance may lead to relapse Consider stopping lithium for up to 7 days if the patient becomes acutely and severely ill with a metabolic or respiratory disturbance from whatever cause 2 Women of childbearing age should use reliable contraception. If the pregnancy is confirmed in the 1st trimester, and the woman is stable, lithium should be stopped gradually over 4 weeks, and the woman informed that this may not remove the risk of cardiac defects in the fetus. 2 If a woman remains on lithium during pregnancy more frequent monitoring is required, and good fluid intake is essential 2 Long term adverse effect Long term treatment with lithium may be associated with persistent parathyroidism and hypercalcaemia, weight gain, changes in glucose tolerance, nephrogenic diabetes insipidus, nephritic syndrome. In some patients goitre can be induced as lithium can inhibit thyroid hormone release. Hypothyroidism can be successfully managed with thyroxine. Lithium is also teratogenic 12 Hypothyroidism There is a small risk that people taking lithium at therapeutic doses may develop clinical goitre, hypothyroidism, or both; the risk appears to be greatest in the first Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 10 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring 2 years of treatment. Although this may occur, it should not be a reason for stopping lithium treatment. Levothyroxine replacement is usually indicated. Thyroxine function tests usually return to normal when lithium is discontinued. 9 Lithium treatment increases the risk of clinical hypothyroidism up to five-fold, the risk being particularly high in women who are 40-59 years old.9 The clinical symptoms of hypothyroidism overlap with those of depression and may therefore remain undiagnosed and untreated unless specific screening tests are undertaken. 4 Hyperthyroidism Lithium-associated thyrotoxicosis is rare and occurs mainly after long-term use. It should not constitute an absolute contraindication to lithium treatment. Specialist advice should be sought regarding management. 9 Hyperparathyroidism Lithium use has been associated with hypercalcaemia accompanied by elevations in circulating parathyroid hormone (PTH). The coexistence of hypercalcaemia and elevated PTH levels suggests primary hyperparathyroidism. However, significantly greater serum levels of calcium are probably required to inhibit PTH secretion during lithium therapy. The presence of mild hypercalcaemia with elevated PTH is consistent with lithium-induced hyperparathyroidism. Parathyroid surgery is not indicated in this situation, and withdrawal of lithium will result in prompt normalization of serum calcium and PTH levels. 9 Nephrotoxicity A small reduction in glomerular filtration rate is seen in 20% of people taking lithium. In the vast majority of these people this effect is benign. A very small number of people taking lithium may develop interstitial nephritis. Lithium can also cause a reduction in urinary concentrating capacity (nephrogenic diabetes insipidus, with symptoms of thirst and polyuria) which is reversible in the short-to-medium term, but may be irreversible after long-term treatment (greater than 15 years). 9 Stopping Lithium Lithium should be stopped gradually over at least 4 weeks 1, and preferably over a period of up to 3 months, particularly if the patient has a history of manic relapse (even if they have been started on another antimanic agent). 2,3,6 When lithium treatment is stopped or is about to be stopped abruptly, prescribers should consider changing to monotherapy with an atypical antipsychotic or valproate, and then monitor closely for early signs of mania and depression. 2 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 11 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Appendix B – Lithium Shared Care Protocol Abertawe Bro Morgannwg (ABM) Health Authority DRUG: LITHIUM CARBONATE (Priadel tablets, Camcolit tablets, Liskonum tablets) LITHIUM CITRATE (Li-liquid, Priadel liquid) This document should be read in conjunction with the current Summary of Product Characteristics (SPC) http://www.medicines.org.uk/ This protocol is part of an enhanced service. INDICATIONS FOR LITHIUM THERAPY Treatment and prophylaxis of mania, bipolar disorder, and recurrent depression, aggressive or self-mutilating behaviour GENERAL GUIDANCE This protocol sets out details for the monitoring of patients requiring lithium and should be read in conjunction with the Lithium Monitoring Service Specification. Sharing of monitoring requires communication between the specialist, GP and patient. The intention to share monitoring of lithium treatment should be explained to the patient by the doctor initiating treatment. The doctor who prescribes the medication legally assumes responsibility for the drug and the consequences of its use. The prescriber has a duty to keep themselves informed about the medicines they prescribe, their appropriateness, effectiveness and cost. They should also keep up to date with the relevant guidance on the use of the medicines and on the management of the patient’s condition. BACKGROUND Lithium is licensed for use in the management of acute manic or hypomanic episodes, the prophylaxis of bipolar affective disorder, and the management of episodes of recurrent depressive disorders where treatment with other antidepressants has been unsuccessful. It is also licensed for control of aggressive behaviour or intentional selfharm. Lithium has small therapeutic index and plasma levels may be affected by many factors. Lithium toxicity is potentially fatal. For this reason regular monitoring of lithium levels is required. CRITERIA FOR SHARED CARE Prescribing responsibility will only be transferred when: Treatment is for a specified indication and duration; Treatment has been initiated and stabilised by the secondary care specialist; The patient’s initial reaction to and response on the drug is satisfactory; The GP has agreed in writing in each individual case that primary care lithium monitoring is appropriate; The patient’s general physical, mental and social circumstances are such that he/she would benefit from this arrangement. RESPONSIBILITIES OF INITIATING CONSULTANT Confirm diagnosis, and assess baseline mental state; Ensure all baseline monitoring is undertaken; Initiate lithium treatment if patient deemed suitable in terms of diagnosis and Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 12 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales 1 Lithium Monitoring fitness for medication; Review and Stabilisation of patient on Lithium. Until stable (lithium level and dose both stable for 4 weeks), prescribing should be confined to secondary care. Monitor patient’s initial reaction to and progress on the drug; Request for monitoring to be shared with GP. Once stable, prescribing and monitoring of lithium will be via General Practitioner (for this reason it is imperative all lithium monitoring results are shared in writing between Health Board Mental Health department and General Practitioner); Contact the GP to invite participation in monitoring of lithium by sending the Lithium Monitoring Agreement. The Health Board recognises that the GP has the right to refuse to participate in sharing of care. In such an event the total clinical responsibility for the patient for the diagnosed condition will remain with the consultant; Secondary care will provide patient with: o NPSA patient information booklet or other relevant drug information to enable informed consent to therapy, understanding of potential side effects & appropriate action, & an understanding of the role of monitoring; o Completed NPSA record book & Lithium card1 on initiation of treatment; o Record book must be given to patient to take to all appointments; Arrange for hospital supply of medication until in the opinion of the consultant the patient's condition is stable; Ensure that the patient has an adequate supply of medication until GP supply can be arranged; Monitor patient’s initial reaction to and progress on the drug; Ensure that serum lithium monitoring is carried out during initial titration and during periods of instability either in secondary care or by arrangement with GP; On receipt of the GP's agreement the consultant will supply a complete patient summary. The summary will provide the information specified in the appropriate protocol. Full details of all other drugs will be given. An original pack supply of the drug will be dispensed by the hospital (unless a smaller quantity is appropriate). Ensure that the patient has an adequate supply of medication until GP supply can be arranged; Secondary care will arrange regular out-patient assessment depending on clinical circumstances and will see the patient at the GP's request. The assessments will include clinical monitoring as set out in this protocol, consideration of potential drug interactions, assessment of compliance & response, and evaluation of any adverse events noted by the patient/carer or GP; Communication - Secondary care will provide GP with: o Diagnosis, relevant clinical information and baseline results, treatment to date and treatment plan, intervals for consultant review, and any change in the patient's status including the dose, target blood range, frequency and form of the drugs currently prescribed; o Provide GP with details of outpatient consultations, ideally within 14 days of seeing the patient or inform GP if the patient does not attend appointment; o Advice on when to stop this drug including urgent advice in response to abnormal blood results identified during monitoring. http://www.nrls.npsa.nhs.uk/resources/?entryid45=65426&q=0%c2%aclithium%c2%ac Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 13 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring RESPONSIBILITIES OF PRIMARY CARE Complete the “Lithium Monitoring Agreement Form”; Following receipt of the “Lithium Monitoring Agreement Form” and reference to the Lithium Monitoring Protocol the GP should ensure they have the information and knowledge to understand the therapeutic issues relating to the patients medical condition and the facilities to comply with the protocol; Return the completed “Lithium Monitoring Agreement Form” within one week of receipt of the request to indicate whether the GP is willing to undertake lithium monitoring Prescribe the maintenance therapy in accordance with the consultant request, whilst also considering potential drug interactions. This may include changing the dose of medication as advised by hospital specialist team; Monitor and record the therapy in accordance with the lithium monitoring protocol; To ensure that the lithium record book is kept up to date; Record and communicate with secondary care all symptoms or results that are appropriate; Report any adverse events in the treatment of the patient to the consultant, as well as to the usual bodies- including the locality clinical governance lead (e.g. yellow card reporting to CSM); Monitor the patient for signs of toxicity and take immediate action as appropriate (see below). RESPONSIBILITIES OF PATIENT / SERVICE USER Attend hospital and GP clinic appointments, bringing lithium record booklet (once issued); Failure to attend will result in referral back into secondary care management and potentially medication being stopped (on specialist advice); Report adverse effects to their specialist or GP, urgently if any of the following occur: ataxia, coarse tremor, dysarthria , confusion, lack of co-ordination. ADDITIONAL CONSIDERATIONS There may be a very gradual increase in serum lithium level over time, probably because of progressive reduction in renal function with age; Renal disease can reduce elimination of lithium and doses may need to be reduced; Renal lithium concentration is usually constant, however, when plasma concentration is low, or the patient is dehydrated, lithium clearance falls and blood levels rise relative to glomerular filtration rate. Accordingly lithium levels are likely to be increased in a patient with a low salt diet, on a drug which reduces lithium excretion, e.g. NSAID (including COX-2s), ACE inhibitor, diuretic, or who has diarrhoea, vomiting or excessive sweating; Patients should maintain an adequate fluid intake and should avoid dietary changes which might reduce or increase sodium intake; The ABMU Health Board “Early Intervention Project” strongly advises patients admitted to Medical and Surgical wards to be referred for senior psychiatric opinion with patient’s consent, at earliest opportunity. CONTRAINDICATIONS Hypersensitivity to lithium or to any of the excipients. Lithium is not recommended in pregnancy or breast-feeding. Women of childbearing age should be advised to use reliable contraception. Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 14 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring See current Summary of Product Characteristics for full list. DOSAGE REGIMEN For full prescribing information please consultant the Summary of Product Characteristics for the requested product. These can be found at: http://www.medicines.org.uk/emc/ Route: ORAL Lithium should be started at a low dose and titrated up to achieve therapeutic levels as indicated by serum level monitoring. The normal starting dose in 400mg at night2 of the modified release preparation, lower in the elderly or in renal impairment. The dose should then be adjusted according to serum levels of lithium. The recommended therapeutic range is 0.4-1.0mmol/L. See BNF for dosing regimens specific to different formulations. Lithium has linear pharmacokinetics therefore, assuming stable renal function, an increase in dose of 25% will result in an increase of serum lithium concentration of 25%. Conditions requiring dose reduction Elderly patients OR those below 50kg in weight, often require lower lithium dosage to achieve therapeutic serum levels. Starting doses of 200mg to 400mg are recommended. Dosage increments of 200 to 400mg every 3 to 5 days are usual.3 Formulations: As bioavailability varies from product to product (particularly with regard to retard or slow release preparations) a change of product should be regarded as initiation of new treatment. Lithium is available as the carbonate salt (tablet formulations) and citrate salt (liquid preparation). As a general guide lithium carbonate 200mg = lithium citrate 509mg, however, changing preparation requires the same precaution as initiation of therapy. The default product for all patients newly commenced on lithium within ABMU HB is Priadel unless stated otherwise. Priadel is available in 200mg (5.4mmol Li+) & 400mg modified release scored lithium carbonate tablets and 520mg/5ml (5.4mmol Li+) lithium citrate liquid. Lithium citrate liquid & Liskonium® tablets should be administered twice daily. Other lithium preparations are normally prescribed as a single dose at night. All dose adjustments will be done by secondary care unless directions have been specified in the medical letter to the GP. BASELINE MONITORING Mental state. Smoking status and alcohol intake. Baseline investigations (Pre-treatment) - to be undertaken by secondary care4: Thyroid function tests (TSH & T4); Taylor D, Paton C, Kerwin R. The Maudsley Prescribing Guidelines. 9 th Ed. London: Informa Uk Ltd; 2007. p148 3 Sanofi Aventis. SPC Priadel 200mg & 400mg prolonged release tablets.[Online]. Available from: http://emc.medicines.org.uk/document.aspx?documentId=6983 [Accessed 27th October 2009]. 4 National Institute for Clinical Excellence. Bipolar Disorder. The management of bipolar disorder in adults, children & adolescents, in primary & secondary care. Clinical Guideline 38. htt:p//www.nice.org.uk. 2006. 2 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 15 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Renal function (U&Es, eGFR5, serum creatinine); Full Blood Count; Liver Function Tests (LFTs) & Bone Profile; Body mass index (BMI); Blood pressure; Lipid profile; Blood (plasma) glucose; ECG (for those with existing cardiac disease or risk factors)6. When indicated by the clinical picture or co-morbidity Drug screening, CXR, EEG,MRI, CT. MONITORING This monitoring protocol is based upon a principle of minimum regular 3 monthly lithium levels carried out in primary care for all patients prescribed lithium by their GP. Additional Monitoring by Secondary Care: It is recognised that the frequency of testing may need to be increased depending on individual patient risk, however, additional testing above and beyond the 3 monthly lithium levels monitored in primary care should be undertaken by secondary care. In such cases it is imperative that secondary care checks results of primary care testing to avoid duplication of monitoring. It is imperative that GP maintains baseline monitoring of lithium levels every 3 months. 5 6 Kripalani M, Shawcross J, Reilly J, Main J. Lithium and chronic kidney disease. BMJ 2009;339:166-9 Taylor D, Paton C, Kerwin R. The Maudsley Prescribing Guidelines. 9th Ed. London: Informa Uk Ltd; 2007. p148 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 16 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring This monitoring protocol requires minimum regular 3 monthly lithium levels carried out in primary care for all patients prescribed lithium by their GP Monitoring Frequency Action Responsibility Serum lithium levels (initial) Serum lithium levels (once stable) Thyroid function tests (TSH &T4) Renal function (U&Es, eGFR, serum creatinine) Full Blood Count Liver Function Tests & bone profile BMI Blood Pressure Lipid profile (over 40s only) Blood (plasma) glucose Review of mental health & monitoring 5-7 days after initiation then weekly until dose and serum lithium levels stable (Stable defined as steady for 4 weeks) Once stable, every three months minimum Six monthly (three monthly if evidence of deterioration) Six monthly (more often if evidence of deterioration or other medication changed e.g. nsaid/diuretic/ACE) Only if clinically indicated Only if clinically indicated Secondary Care / Consultant Psychiatrist Primary Care / GP All requests to pathology must state the secondary care consultant or team to be copied into results, for interpretation and dosing advice Primary Care / GP Primary Care / GP Primary Care / GP Primary Care / GP Annually – more frequently if patient gains weight rapidly Annually Annually Primary Care / GP Primary Care / GP Primary Care / GP Annually Primary Care / GP Annually Secondary Care / Consultant Psychiatirst Where it is not possible/ appropriate in certain patients to perform regular additional blood tests within secondary care lithium clinic, the GP may be asked to participate in carrying out these recommended blood tests. Therapeutic Drug Monitoring: Blood samples for lithium should be taken 12 hours after the last dose. There can be diurnal variation, so ideally the sample should be taken at the same time on each occasion. Therapeutic levels should be 0.4-1.0mmol/L. Whoever initiates blood tests for lithium blood levels is responsible for acting on abnormal lithium results. Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 17 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring ADVERSE EFFECTS In addition to carrying out the regular recommended blood test monitoring, it is important to note that it is also the prescriber’s responsibility to ensure that patients are monitored for signs and symptoms of toxicity and potential adverse effects according to the summary of product characteristics. Side effects are usually related to serum lithium concentration and are less common in patients with plasma lithium concentrations below 1.0 mmol/l. Long term treatment with lithium may result in permanent changes in the kidney and impairment of renal function. High serum concentrations of lithium, including episodes of acute lithium toxicity may enhance these changes. See SPC for full list of reported adverse reactions. Clinical condition (Where possible indicate if common, rare or serious) Initial therapy fine tremor of the hands, dry mouth, metallic taste in mouth polyuria and thirst may occur Dermatology alopecia, acne, folliculitis, pruritus, aggravation or occurrence of psoriasis, allergic rashes, acneiform eruptions, papular skin disorders, cutaneous ulcers. Endocrine euthyroid goitre, hypothyroidism, hyperthyroidism and thyrotoxicosis. Lithium-induced hypothyroidism may be managed successfully with concurrent levothyroxine. Hypercalcaemia, hypermagnesaemia, hyperparathyroidism have been reported Gastrointestinal anorexia, nausea, vomiting, diarrhoea, excessive salivation, dry mouth, abdominal discomfort, taste disorder, gastritis Haematological leucocytosis Metabolic & weight gain, hyperglycaemia Nutritional Renal polydipsia and/or polyuria, symptoms of nephrogenic diabetes insipidus, histological renal changes with interstitial fibrosis after long term treatment. High serum concentrations of lithium including episodes of acute lithium toxicity may aggravate these changes. The minimum clinically effective dose of lithium should always be used. In patients who develop polyuria and/or polydipsia, renal function should be monitored, e.g. with measurement of blood urea, serum creatinine and urinary protein levels in addition to the routine serum lithium assessment Reproductive sexual dysfunction Senses dysgeusia, blurred vision, scotomata Cardiovascular Effects of lithium are rare and often benign. Reported effects are arrhythmia, oedema and sinus node dysfunction. QT interval prolongation, ventricular arrhythmias – ventricular fibrillation, ventricular tachycardia (rare), sudden unexplained death, cardiac arrest and Torsade de pointes have been reported, Any signs of cardiac disturbance e.g. syncope, heart rhythm or rate disturbances should be investigated further Rare cases Nephritic syndrome, speech disorder, confusion, impaired consciousness, myoclonus and abnormal reflex have been reported. If any of the above symptoms appear, treatment should be stopped immediately & arrangements made for serum lithium measurement Author: Primary Care Quality and Date: February Status; Final Information Service 2012 Intended Audience; Public Lithium Monitoring; Version 1 18 (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Serious toxicity may present first to GPs. IF YOU SUSPECT LITHIUM TOXICITY, STOP THE DRUG AND CONTACT THE CONSULTANT PSYCHIATRIST/ SECONDARY CARE MENTAL HEALTH TEAM. IF CLINICAL CONDITION WARRANTS REFER TO NEAREST ACCIDENT & EMERGENCY DEPARTMENT. IF YOU SUSPECT AN ADVERSE REACTION HAS OCCURRED, PLEASE CONTACT THE CONSULTANT PSYCHIATRIST/ SECONDARY CARE MENTAL HEALTH TEAM. All serious adverse drug reactions should be reported to the CSM via “Yellow Card” scheme IMMEDIATELY. Blood sample should be taken immediately to determine serum lithium levels, renal function, FBC, & LFTs. The GP may also refer to the nearest accident and emergency department if the clinical condition warrants it. Lithium toxicity can occur at any serum lithium level but particularly at levels >1.5mmol/L. It is particularly important for GPs to check for ataxia, dysarthria &/or lack of coordination as these have been found to be clinically useful symptoms indicating lithium toxicity7 Symptoms of lithium toxicity include; anorexia, diarrhoea, vomiting, muscle weakness, muscle twitching, tinnitus, blurred vision, ataxia, coarse tremor, dysarthria, confusion, lack of co-ordination and in severe toxicity, stupor, coma, renal impairment, cardiac arrhythmias and death. If features of lithium toxicity occur stop lithium immediately, check serum lithium levels, creatinine, urea and electrolytes and discuss with a doctor from mental health services. Refer to the nearest accident and emergency department if the clinical condition warrants it. INTERACTIONS Caution is advised when any patient is co-prescribed interacting medications with lithium and specialist advice should be sought if needed. The following are important drug interactions: Diuretics, loop & especially thiazides reduce lithium excretion, and increase serum levels leading to toxicity. Refer to secondary care for specialist advice and dose reduction prior to initiating a diuretic. Re-stabilisation will be required; NSAIDs (including COX-2s) reduce lithium excretion, increasing lithium serum levels which can lead to toxicity. Avoid PRN (when required) use of NSAIDS. SSRIs - increased risk of CNS toxicity; ACE inhibitors - may alter lithium excretion; Sodium containing antacids - reduce lithium levels. To compensate, the patient’s dose may have been increased. If the patient then stops taking the antacid toxicity may occur. Please see SPC for full details before initiating any new medication In principle if a drug acts on or through the kidney, or affects sodium levels, an interaction is possible. When assessing potentially interacting medication consider: 7 Colgate R. Ranking of therapeutic and toxic side-effects of lithium carbonate. Psychiatric Bulletin 1992;16:473-475 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 19 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring if lithium levels are being monitored more frequently. if the use of the drugs is occasional (PRN). You may need to advise a patient of the potential harm of using an interacting drug occasionally. if lithium dosing has been altered to compensate for interacting drugs. Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 20 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Lithium Monitoring Agreement Form CONSULTANT REQUEST TO GP - *IMPORTANT: ACTION NEEDED To: Dr. Name of patient___________________________________________ Date of birth _________________ Diagnosed condition ____________________________________________________________________ This patient has been accepted as suitable for Lithium monitoring in accordance with the attached protocol. I am requesting your agreement to share the lithium monitoring of this patient. The preliminary tests set out in the protocol have been carried out. I am currently prescribing the stabilising treatment. I would like you to undertake treatment from (date): __________________________________________ The initial treatment will be: ______________________________________________________________ _____________________________________________________________________________________ The baseline tests are: __________________________________________________________________ _____________________________________________________________________________________ If you undertake treatment I will reassess the patient in __ weeks. You will be sent a written summary within 14 days. I will accept referral for reassessment at your request. The medical staff of the department are available at all times to give you advice. Contact Telephone No. __________________________________________________________________ Consultant Name_______________________________________________________________________ Signature ____________________________________________________________________________ Department ________________________________________________ Date _____________________ Hospital ______________________________________________________________________________ GP RESPONSE A. I am willing to undertake Lithium shared care as set out in the protocol for this patient. B. I wish to discuss this request with you. C. I am unable to undertake shared care for this patient. G.P. signature______________________________________________________ Date ______________ Practice Address/Stamp _____________________________________________________________________________________ (Please return whole completed form or a photocopy to the consultant requesting shared care prescribing within one week). Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 21 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Appendix C- Further Information Lithium Therapy: Manic depression fellowship Wales Monitoring patients on lithium – a good practice guideline 2002 General Practice Notebook - Lithium How safe is lithium prescribing? The Psychiatrist 2005 Scottish shared care guidance for GP’s 2009 MIND Making sense of Lithium and other mood stabilisers Lithium in breast milk and nursing mothers: Clinical implications electronic Medicines Compendium (eMC) Priadel Clinical effectiveness group (ceg); Severe Long-term Mental Health Problems 2003 The primary care guide to managing severe mental illness 2004 Adult Mental Health Services in Primary Healthcare Settings in Wales Welsh Health Circular WHC (2006) 053 NHS Primary Care guidelines; Bipolar Disorder F31 2004 Lithium: Shared care Protocol and Information for GP’s; Scotland 2009 Better testing: Lithium safety monitoring 2005 Lithium for maintenance treatment of bipolar disorders: bipolar foundation Long term lithium therapy for bipolar disorder: Systematic review and metaanalysis of randomised controlled trials 2004 Lithium for maintenance treatment of mood disorders; Cochrane systematic review 2001 Lithium verses antidepressants in the long term treatment of unipolar affective disorder: Cochrane systematic review 2006 Suicidal risks during treatment of bipolar disorder patients with lithium verses anticonvulsants: DARE review 2010 Prescribing Observatory for Mental Health (POMH-UK) Monitoring patients on lithium in the primary care setting 2004 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 22 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Using Lithium Safely DTB Vol 37 No 3 March 1999 GPC acts over lithium quality confusion 2005 Lithium treatment and thyroid abnormalities 2006 Wales Mental Health in Primary Care Network Primary Care guide to Managing Severe Mental Illness 2004 Long-term Lithium Therapy Leading to Hyperparathyroidism: A Case Report 2009 eMC Medicine Guide SPC Priadel 2011 Lithium-induced Hypercalcemia and Parathyroid Dysfunction 2001 Reversible hypercalcemia and hyperparathyroidism associated with lithium therapy: a case report and review of the literature 2006 Lithium: a review of its metabolic adverse effects 2006 Requesting patterns for serum calcium concentration in patients on long-term lithium therapy 2009 Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 23 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Appendix D - READ Codes These suggested read codes may be of help when completing this audit. Please note that the Read Codes below are from Read Code Version 2 (5 Byte) and that the ‘%’ indicates that the code and its children should be included within the search. Lithium Read Code LITHIUM SALTS d6... % Long term drug therapy 8B3G. Diagnosis Read Code [X]Mania NOS Eu30z Affective psychoses E11.. % [X]Bipolar affective disorder Eu31. % Recurrent depression E1137 [X]Mood - affective disorders Eu3.. % Neurotic, personality and other nonpsychotic disorders E2... % Monitoring Read Code Lithium monitoring 6657. Lithium level checked at 3 monthly intervals 665J. Lithium annual review 8BM00 Disorders of thyroid gland C0... Renal function monitoring 8A6.. Body Mass Index 22K.. O/E - BP reading 246.. % Smoker - amount smoked 137.. % Alcohol consumption 136.. % ECG 32... % Pregnancy advice 67A.. % Advice given about lithium side-effects and toxicity 8Cd5. Patient held care plan 9366. Lithium patient information booklet given 8CE90 Lithium therapy record book completed 665K. Psychiatric monitoring 8A2Z. Seen in psychiatric clinic 9N1T. Medication review 8B3S. Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 24 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Management Read Code Drug compliance good 8B3E. Drug compliance poor 8B3i. Prescription dose change 66R5. Medication change to branded 8BP4. Shared care prescribing 8BM5. Prescription by GP 8B2F. Blood Tests Read Code Renal function tests 451.. % Thyroid function tests 442..% Thyroid function tests normal 442H. Thyroid function tests abnormal 442I. Serum creatinine 44J3. % Serum calcium 44I8. % Glomerular filtration rate 451F. Glomerular filtration rate calculated by abbreviated Modification of Diet Renal Disease Study Group calculation Urea in and electrolytes 451E. Urea and electrolytes normal 44120 Urea and electrolytes abnormal 44121 Blood Levels 44JB. Read Code Serum lithium level 44W8. % Lithium level therapeutic 44vE. [D]Lithium, blood level abnormal R1053 Lithium level high - toxic 44W81 Interactions Read Code Non-steroidal anti-inflammatory drugs contraindicated 8I2T. Angiotensin converting enzyme inhibitors contraindicated 8I28. [X] Adverse reaction to other diuretics U60E5 [X]Fluoxetine adverse reaction U609A Advice regarding symptoms on discontinuation of selective serotonin re-uptake inhibitor 8CAh. Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 25 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Appendix E - Quality improvement toolkit – evaluation form Quality improvement toolkit - evaluation form The Primary Care Quality and Information Service would like to ensure that the information and suggested tools help practices to monitor and audit their practice data, therefore please could you take a moment and provide your comments on the quality improvement toolkit. 1) Did you find the introduction, aims and methodology to be clear and easy to understand? YES NO If No, please comment _______________________________________ 2) Did you find the Audit Criteria to be clear and easy to understand? YES NO If No, please comment _______________________________________ 3) Did you find the data collection easy to use? YES NO If No, please comment _______________________________________ 4) Did you find the data summary easy to usel? YES NO N/A If No, please comment _______________________________________ 5) Did you find the practice review template useful? YES NO N/A If No, please comment _______________________________________ 6) Did you find the information within the appendices helpful? YES NO If No, please comment ______________________________________ 7) Do you have any suggestions on how we should improve our quality improvement toolkits? __________________________________________________________ __________________________________________________________ __________________________________________________________ Please send to: Laura Jones PCQIS Public Health Wales 36, Orchard Street, Swansea. SA1 5AQ e-mail [email protected] Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 26 Intended Audience; Public (internet) / NHS / PHW / PCQIS Public Health Wales Lithium Monitoring Appendix F - References 1. British Association of Psychopharmacology: Evidence bases guidelines for treating bipolar disorder: revised second edition recommendations 2009 http://www.bap.org.uk/pdfs/Bipolar_guidelines.pdf 2. NICE Bipolar disorder Clinical guideline 38 2006 http://www.nice.org.uk/nicemedia/live/10990/30193/30193.pdf 3. SIGN Bipolar affective disorder: 82; May 2005 http://www.sign.ac.uk/pdf/sign82.pdf 4. NPSA Safer lithium therapy 2009 http://www.nrls.npsa.nhs.uk/resources/?EntryId45=65426 5. Drug Monitoring Toolkit PCQIS page 58 Lithium 2008 http://nww2.nphs.wales.nhs.uk:8080/primarycareqitdocs.nsf/1f8687d 8da97650980256fa30051b0be/3e75f1384cd148a7802575050033306a /$FILE/2009%20Drug%20Monitoring%20LoRes%20for%20Web.pdf 6. Gwent Healthcare NHS Trust Policy for the Use and Administration of Lithium http://www.wales.nhs.uk/sites3/Documents/814/Lithium%2DGwentTr ustPolicyJune2009.pdf 7. MHRA Lithium Overdose http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicin es/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/ Genericoverdosesections/Lithium/CON026247 8. GMS Contract Lithium indicators page 78 Quality & Outcome Framework guidance for GMS contract 2009/10 http://www.wales.nhs.uk/sites3/Documents/480/QOF%5FGuidance%5 F2009%2D10%5FFINAL.pdf 9. CKS Bipolar Disorder – Management - Lithium 2009 http://www.cks.nhs.uk/bipolar_disorder/management/prescribing_info rmation/lithium/monitoring 10. BNF 60 September 2010 Lithium: 4.2.3 Antimanic drugs; page 223 http://bnf.org/bnf/bnf/current/3281.htm?q=Lithium&t=search&ss=text &p=2#_hit 11. NICE The treatment and management of depression in adults: Update 2009 http://www.nice.org.uk/nicemedia/live/12329/45888/45888.pdf 12. Lithium: Cardiff and Vale Shared Care Policy CV12 2010 http://www.wmic.wales.nhs.uk/pdfs/shared_care_protocols/lithium_sc _cv12_v4.0_nov2010.pdf Author: Primary Care Quality and Information Service Date: February 2012 Status; Final Lithium Monitoring; Version 1 27 Intended Audience; Public (internet) / NHS / PHW / PCQIS