The anti-manic properties of lithium were first discovered by Australian psychiatrist John Cade in 1949. It is a mood stabiliser and has numerous effects on biological systems. It can substitute for sodium, potassium, calcium and magnesium in biological systems and enters the cells and interferes with transmitter release and second messenger systems. Hence, it can block release of certain transmitters and hormones.
NB: unsuitable for children.
- Management of acute manic or hypomanic episodes.
- Prophylaxis of bipolar (manic-depressive) illness (co-administration of antidepressants may be needed in a depressive phase)[3, 4]. Lithium is highly effective at reducing both relapses (particularly manic episodes) and suicide rate[5, 6].
- Prophylaxis of recurrent depression and schizoaffective disorder.
- Augmentation of the antidepressant effect when it is co-prescribed with antidepressants in acute depressive illness.
- Prophylaxis of cluster headache (unlicensed indication)[8, 9].
- Control of aggressive behaviour or intentional self-harm and possibly suicidal behaviour. Lithium has been used successfully to reduce aggression in patients with learning disabilities who are unmanageable by environmental factors, and in patients with aggressive self-mutilating behaviour.
Before starting lithium
- Discuss with a psychiatrist - lithium should only be started under specialist supervision, weighing up the risks and benefits.
- If the patient is dangerously manic, refer for urgent admission.
- Lithium has a slow onset of action (7-14 days) so an antipsychotic may be needed initially - eg, haloperidol.
- Perform the following baseline tests:
- Measure weight, blood pressure and pulse.
- Ensure renal function is normal, as lithium is primarily excreted by the kidney. Measure serum creatinine, eGFR and possibly urine albumin:creatinine ratio (see reference for a good algorithm to follow).
- Check FBC, U&E, creatinine, TFT, calcium. NB: plasma lithium levels are increased by sodium depletion(competitive reabsorption at the renal level).
- Check there is no goitre; take blood for thyroid autoantibodies where there is a family history of thyroid disorders.
- It may be worth measuring baseline parathyroid hormone and magnesium.
- Perform baseline ECG.
Important drug interactions
Avoid any medicines that can impair renal function or induce hyponatraemia (see monograph). Seek specialist advice:
- Angiotensin-converting enzyme (ACE) inhibitors.
- Diuretics (particularly thiazides).
- Non-steroidal anti-inflammatory drugs (NSAIDs).
- Selective serotonin reuptake inhibitors (SSRIs) - sometimes co-prescribed.
- Cardiac disease.
- Significant renal impairment.
- Addison's disease and patients with low body sodium levels.
- Untreated hypothyroidism.
Pregnancy and breast-feeding
- Pregnancy: avoid in the first trimester (teratogenic). Only use in the second and third trimester if considered essential (ie a severe risk to the patient) and monitor levels closely, as dose requirements may alter.
- Breast-feeding: avoid, as present in milk and there is risk of toxicity in an infant. Bottle-feeding is advisable.
- Always prescribe non-generically by brand name - preparations may vary widely in bioavailability.
- Inform patients:
- Of potential toxicity and symptoms of this (see 'Side-effects and toxicity', below).
- That they should ensure they have a regular fluid intake.
- Of the need for compliance in taking medication - reinforce this and that they should not stop or omit doses.
- Of the dangers of crash diets.
- To avoid NSAIDs.
- Not to exceed more than 1-2 units of alcohol per day.
- That it takes 3-6 months to be established on lithium.
- That lithium cards are available from pharmacists.
- The initial dose will depend on weight - use a lower dose in elderly patients.
- Check lithium levels (12 hours following dose):
- Five days following starting therapy or changing a dose.
- Then check levels weekly until levels have been stable for four weeks.
- Once levels have stabilised, check lithium levels every three months.
- Consider more frequent monitoring (eg, every two months) in the elderly, in those on interacting medication or in those with renal, thyroid or cardiac disease.
- Target concentrations:
- Acute episode (mania, hypomania, depression) 0.6-1.0 mmol/L (elderly 0.4-0.8 mmol/L).
- Prophylaxis of bipolar affective disorder 0.4-0.8 mmol/L.
- Toxic range usually >1.5 mmol/L; however, may begin at >1.0 mmol/L (levels >2 mmol/L need urgent treatment).
Monitoring lithium treatment
Many PCTs have agreed shared care protocols:
- Check lithium levels (12 hours post-dose) at least every three months and during any intercurrent illness (can increase and cause toxicity).
- Therapeutic lithium levels: 0.4 to 1.0 mmol/L (may vary from laboratory to laboratory).
- At each consultation, ask about any signs of toxicity or signs of hypothyroidism.
- Check thyroid function, U&Es, calcium and creatinine (and possibly urine dipstick for protein) every 6-12 months.
Side-effects and toxicity
- Lithium levels >1.5 mmol/L (>2.0 mmol/L may be associated with serious toxicity).
- Lithium toxicity should also be suspected at 'therapeutic' levels in compromised patients with relevant symptoms.
These can usually be reduced or eliminated by lowering the lithium dose or changing the dosage schedule:
- Abdominal pain.
- Metallic taste in the mouth (usually wears off).
- Fine tremor.
- Thirst, polyuria, impaired urinary concentration - avoid fluid restriction.
- Weight gain and oedema.
- Cognitive impairment - presents as memory deficits, mild drowsiness.
- Hyperparathyroidism and hypercalcaemia.
- Nephrogenic diabetes insipidus.
Toxicity may be due to intentional overdose but it usually occurs during chronic treatment because of reduced drug excretion (dehydration, worsening renal function, concurrent infections, and drug interactions).
Stop lithium, check level and refer for urgent assessment (encourage fluids, stop diuretics, monitor electrolytes and monitor renal function).
- Anorexia, diarrhoea and vomiting.
- Drowsiness, apathy, restlessness.
- Dizziness, ataxia, inco-ordination, muscle twitching, coarse tremor.
Admit as an emergency (whole bowel irrigation may be considered if large quantities have been ingested).
- Hyperreflexia, convulsions.
- Collapse, coma.
- Renal failure, dehydration, circulatory collapse (may need haemodialysis).
Abrupt withdrawal (both because of poor compliance or rapid change in dose) can precipitate relapse. Withdraw lithium slowly over several weeks, watching for relapse.
Further reading and references
Safer Lithium Therapy; National Patient Safety Agency (2009)
Cade JF; Lithium salts in the treatment of psychotic excitement. 1949. Bull World Health Organ. 2000
Summary of Product Characteristics (SPC) - Priadel® 200 mg prolonged release tablets; Sanofi, electronic Medicines Compendium, June 2015
Lithium Shared Care Protocol and Information for GPs; NHS Fife, January 2013
Bipolar disorder - the assessment and management of bipolar disorder in adults children and young people in primary and secondary care; NICE Clinical Guideline (Sept 2014, updated 2016)
Cipriani A, Pretty H, Hawton K, et al; Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry. 2005 Oct162(10):1805-19.
Geddes JR, Burgess S, Hawton K, et al; Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry. 2004 Feb161(2):217-22.
Depression in adults: recognition and management; NICE Clinical Guideline (April 2016)
Headaches in over 12s: diagnosis and management; NICE Clinical Guideline (September 2012)
Capobianco DJ, Dodick DW; Diagnosis and treatment of cluster headache Semin Neurol. 2006 Apr
Terao T; Aggression, suicide, and lithium treatment. Am J Psychiatry. 2008 Oct165(10):1356-7
Leucht S, Kissling W, McGrath J; Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2004 Feb65(2):177-86.
Leucht S, McGrath J, Kissling W; Lithium for schizophrenia. Cochrane Database Syst Rev. 2003(3):CD003834.
Kripalani M, Shawcross J, Reilly J, et al; Lithium and chronic kidney disease. BMJ. 2009 Jul 3339:b2452. doi: 10.1136/bmj.b2452.
Management of Women with Mental Health Issues during Pregnancy and the Postnatal Period; Royal College of Obstetricians and Gynaecologists (June 2011)
McKnight RF, Adida M, Budge K, et al; Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012 Feb 25379(9817):721-8. doi: 10.1016/S0140-6736(11)61516-X. Epub 2012 Jan 20.
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