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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:
The former Public Health Wales Primary Care Quality Team, now incorporated within the Primary and Community Care Development and Innovation Hub, developed a series of quality improvement toolkits to assist practices in collating and reviewing information. From information received, practices still find these toolkits useful, therefore they will remain on this webpage for your ease of reference. Please note, however, that the date of publication is clearly stated in the toolkit and that the evidence within may have changed since publication.
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

Contents

Appendix Page

ALithium Monitoring3-12

BLithium Shared Care Protocol13-22

CFurther Information23 -24

DREAD Codes25-26

EEvaluation Sheet27

FReferences 28

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.

Appendix A – 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 weight1,2,5,9
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). 5,9,10
(ii) Lithium Citrate supplied as a liquid (Priadel and Li-Liquid). 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.1All 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.3

Lithium should be prescribed at an appropriate dose with a daily dosing regimen.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
A serum lithium level of 0.6–0.8mmol/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 lithium1 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 4
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

The NPSA has developed a patient information booklet, lithium alert card and record book for tracking blood tests. 4 Copies are available:mailto:

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

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 levels2
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, non-steroidal 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 annually5,6
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

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 contra-indicated 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 continuedon 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

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 ofthe 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 sub-threshold 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.2

Overdose7

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

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 distress3,4,10, 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

thiazides and related diuretic;
ACE inhibitors
non-steroidal anti-inflammatory drugs (NSAIDS);
sodium bicarbonate containing, non-prescription antacids or urinary alkalinising agents 4

Concomitant use may cause lithium toxicity or with sodium containing antacids sub-therapeutic 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 –5days. Loop diuretics also cause lithium retention but are less likely to result in lithium toxicity 9,12

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 possible12
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 (0.6–1.0mmol/L) and the haloperidol dose is not increased rapidly above the recommended maximum, the chance of inducing a toxic state is very low9

Carbamazepine
In combination with lithium has been reported to cause neurotoxic reactions. Higher (greater than 1mmol/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 / Symptoms10 / Management
Nausea & vomiting
Anorexia, diarrhoea 12
Blurred Vision6
Coarse tremor10
Muscle weakness10
Lack of co-ordination10
Mild drowsiness6
Sluggishness10
Progressive giddiness10
Ataxia6
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 / 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
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. 2If a woman remains on lithium during pregnancy more frequent monitoring is required, and good fluid intake is essential 2

Long term adverse effect