Lithium

Authored by , Reviewed by Dr Colin Tidy | Last edited | Meets Patient’s editorial guidelines

This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Bipolar Disorder article more useful, or one of our other health articles.


Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

The anti-manic properties of lithium were first discovered by Australian psychiatrist John Cade in 1949[1]. 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.

It has been effective in the prevention and treatment of bipolar disorder for over sixty years[2].

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)[4]. Lithium is highly effective at reducing both relapses (particularly manic episodes) and suicide rate  .
  • Prophylaxis of recurrent depression and schizoaffective disorder.
  • Augmentation of the antidepressant effect when it is co-prescribed with antidepressants in treatment resistant depression[5].
  • Prophylaxis of cluster headache (unlicensed indication)[6].
  • 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.

There is no conclusive evidence to support the use of lithium to augment antipsychotic medication in schizophrenia (compared with antipsychotic medication alone)[7].

  • 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 SPC reference below 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)[3].
    • 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.

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.

Pregnancy and breastfeeding[8]

  • 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.
  • Breastfeeding: 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).

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.
  • 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[9].

Common side-effects
These can usually be reduced or eliminated by lowering the lithium dose or changing the dosage schedule:

  • Abdominal pain.
  • Nausea.
  • Metallic taste in the mouth (usually wears off).
  • Fine tremor.
  • Thirst, polyuria, impaired urinary concentration - avoid fluid restriction.
  • Weight gain and oedema.

Less commonly

Toxicity

For full details of treatment consult a National Poisons Information Service centre[10].

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.
  • Dysarthria.
  • Dizziness, ataxia, inco-ordination, muscle twitching, coarse tremor.

Severe toxicity
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).
  • Hypokalaemia.
  • Death.

Additionally ECG changes are noticed[11]. T wave inversion was the most frequently reported ECG finding but other findings include sinus node dysfunction, sinoatrial blocks, PR prolongation, QT prolongation/dispersion, and ventricular tachyarrhythmias. Other cases have shown lithium-treated patients experiencing serious cardiac outcomes, such as ST elevation myocardial infarction and heart blocks. Electrical changes from lithium were found to be dependent on both duration of treatment and the serum lithium level.

Abrupt withdrawal (both because of poor compliance or rapid change in dose) can precipitate relapse. Withdraw lithium slowly over several weeks, watching for relapse.

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Further reading and references

  1. Cade JF; Lithium salts in the treatment of psychotic excitement. 1949. Bull World Health Organ. 2000

  2. Won E, Kim YK; An Oldie but Goodie: Lithium in the Treatment of Bipolar Disorder through Neuroprotective and Neurotrophic Mechanisms. Int J Mol Sci. 2017 Dec 1118(12). pii: ijms18122679. doi: 10.3390/ijms18122679.

  3. Summary of Product Characteristics (SPC) - Priadel® 200 mg prolonged release tablets; Sanofi, electronic Medicines Compendium, June 2015

  4. 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 - last updated 2020)

  5. Cleare A, Pariante CM, Young AH, et al; Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May29(5):459-525. doi: 10.1177/0269881115581093. Epub 2015 May 12.

  6. Brandt RB, Doesborg PGG, Haan J, et al; Pharmacotherapy for Cluster Headache. CNS Drugs. 2020 Feb34(2):171-184. doi: 10.1007/s40263-019-00696-2.

  7. Leucht S, Helfer B, Dold M, et al; Lithium for schizophrenia. Cochrane Database Syst Rev. 2015 Oct 28(10):CD003834. doi: 10.1002/14651858.CD003834.pub3.

  8. Management of Women with Mental Health Issues during Pregnancy and the Postnatal Period; Royal College of Obstetricians and Gynaecologists (June 2011)

  9. 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.

  10. National Poisons Information Service

  11. Mehta N, Vannozzi R; Lithium-induced electrocardiographic changes: A complete review. Clin Cardiol. 2017 Dec40(12):1363-1367. doi: 10.1002/clc.22822. Epub 2017 Dec 16.

Okay so last month my ex had a manic episode and broke up with me thinking its best if we were friends. At that time i didn't know she had bipolar disorder. But then i started looking into it and it...

dennis02079
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