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 - and hence 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. 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).^8,9

• 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 (eg haloperidol).
• Perform the following baseline tests:
  • Measure weight, BP, and pulse.
  • Ensure renal function is normal (with serum creatinine, eGFR and possibly urine dipstick for protein). Lithium is primarily excreted by the kidney.
  • 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 FH of thyroid disorders.
  • It may be worth measuring baseline PTH and magnesium.
  • Perform baseline ECG.

Avoid any medicines that can impair renal function or induce hyponatraemia (see monograph). Seek specialist advice:

• Angiotensin converting enzyme inhibitors
• Diuretics (particularly thiazides)
• NSAIDs
• Selective serotonin re-uptake 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 - 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)
  • They should ensure they have a regular fluid intake
  • Reinforce need for compliance in taking medication - they should not stop or omit doses
  • Of the dangers of crash diets
  • To avoid NSAIDs
  • No more than 1-2 units alcohol per day
  • That it takes 3-6 months to be established on lithium
  • Lithium cards are available from pharmacists.
• Initial dose will depend on weight, use lower dose in elderly
• Check Lithium levels (12 hours post dose):
  • Five 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 months¹⁰
  • Consider more frequent monitoring (eg every 2 months) in the elderly, those on interacting medication or 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; but may begin >1.0 mmol/l (levels >2 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 poisons information 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 renal function).

• Anorexia, diarrhoea and vomiting
• Drowsiness, apathy, restlessness
• Dysarthria
• Dizziness, ataxia, inco-ordination, muscle twitching, coarse tremor.

• Hyper-reflexia, 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.