Lithium

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, 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 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 antidepressant effect when co-prescribed with antidepressants in acute depressive illness.
• Prophylaxis of cluster headache (unlicensed indication).⁷
• Control of aggressive behaviour or intentional self-harm and possibly suicidal behaviour.⁸ 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 is conclusive evidence to support the use of lithium to augment antipsychotic medication in schizophrenia (compared with antipsychotic medication alone).^9,10

• Discuss with psychiatrist - lithium should only be started under specialist supervision, weighing up the risks and benefits.⁶
• If patient is dangerously manic, refer for urgent admission.
• Lithium has a slow onset of action (7-14 days) so may need antipsychotic initially, e.g. 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 good algorithm to follow).¹¹
  • Check FBC, U&E, creatinine, TFT, calcium.
    NB: plasma lithium levels are increased by sodium depletion⁶ (competitive reabsorption at the renal level).²
  • Check there is no goitre, take blood for thyroid autoantibodies if 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:¹¹

• Angiotensin-converting enzyme inhibitors
• Diuretics (particularly thiazides)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Selective serotonin reuptake inhibitors (sometimes co-prescribed)

• Cardiac disease²
• Significant renal impairment
• Addison's disease and patients with low body sodium levels
• Untreated hypothyroidism

Pregnancy and breast-feeding

• Pregnancy - avoid in first trimester (teratogenic). Only use in second and third trimester if considered essential, i.e. severe risk to patient, and monitor levels closely, as dose requirements may alter.
• Breast-feeding - avoid, as present in milk, and risk of toxicity in infant. Bottle feeding advisable.

• Always prescribe non-generically by brand name - preparations may vary widely in bioavailability
• Inform patients:
  • Of potential toxicity and symptoms of this (see below under Side-effects and toxicity)
  • 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
• Initial dose will depend on weight - use lower dose in elderly
• Check lithium levels (12 hours post dose):
  • 5 days following starting therapy or changing dose
  • Then check levels weekly until levels have been stable for 4 weeks
  • Once levels have stabilised, check lithium levels every 3 months¹²
  • Consider more frequent monitoring (e.g. every 2 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 >1.0 mmol/L (levels >2 mmol/L need urgent treatment)

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

• Acne
• Cognitive impairment - presents as memory deficits, mild drowsiness
• Hypothyroidism
• Hyperparathyroidism and hypercalcaemia
• Hypermagnesaemia
• Nephrogenic diabetes insipidus

Toxicity

For full details of treatment consult a National Poisons Information Service centre.
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, incoordination, muscle twitching, coarse tremor

• Hyperreflexia, convulsions
• Collapse, coma
• Renal failure, dehydration, circulatory collapse (may need haemodialysis)
• Hypokalaemia
• Death

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

1. Cade JF; Lithium salts in the treatment of psychotic excitement. 1949.; Bull World Health Organ. 2000;78(4):518-20.
2. Summary of Product Characteristics - Priadel® (Lithium) Sanofi-Aventis; updated Aug 2006; electronic Medicines Compendium
3. Scottish Lithium Shared Care Guideline
4. Cookson J; Use of antipsychotic drugs and lithium in mania.; Br J Psychiatry. 2001 Jun;178(Suppl 41):S148-56. [abstract]
5. 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 Oct;162(10):1805-19. [abstract]
6. 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 Feb;161(2):217-22. [abstract]
7. Capobianco DJ, Dodick DW; Diagnosis and treatment of cluster headache.; Semin Neurol. 2006 Apr;26(2):242-59. [abstract]
8. Terao T; Aggression, suicide, and lithium treatment. Am J Psychiatry. 2008 Oct;165(10):1356-7; author reply 1357.
9. Leucht S, Kissling W, McGrath J; Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials.; J Clin Psychiatry. 2004 Feb;65(2):177-86. [abstract]
10. Leucht S, McGrath J, Kissling W; Lithium for schizophrenia.; Cochrane Database Syst Rev. 2003;(3):CD003834. [abstract]
11. Kripalani M, Shawcross J, Reilly J, et al; Lithium and chronic kidney disease. BMJ. 2009 Jul 3;339:b2452. doi: 10.1136/bmj.b2452.
12. Lithium Shared Care Guideline, Calderdale and Huddersfield, and North Kirklees and Wakefield Area Prescribing Committee; (Accessed May 2007)

• NeLH - Lithium
• MentalHealth.com - Lithium
• MIND - Making sense of Lithium; Patient Information