Lithium

Last updated 20th Dec 2018 - Tom Heaton
Lithium is an inorganic ion used clinically as a mood stabiliser.
It acts in its ionic form to take the place of a number of cations (particularly sodium, also potassium, calcium, magnesium) and so have a number of membrane effects.
This includes impacting on neurotransmitter release.
The exact mechanism of action is not fully understood though.
It is usually only found in trace amounts in humans, arising from dietary sources.

Indications

  • Bipolar disorder - prophylaxis of
  • Mania/hypomania - acute management
  • Depression - prophylaxis
  • Schizoaffective disorder
  • Cluster headache - prophylaxis

It is highly effective at reducing the relapse rate of manic episodes in bipolar disorder.
It also has a notably impact on reducing suicide rates.
It provides no additional benefit to antipsychotic drugs in schizophrenia.
It can augment the antidepressant effects of antidepressant medications.

Pharmacokinetics

Lithium is rapidly absorbed after oral administration.
Oral bioavailability is 100%, with peak plasma levels at around 1-4 hours.

Lithium is excreted by the kidneys.
Elimination can be notably impacted on by impaired renal function or dehydration.
The elimination appears to be biphasic:
  • Rapid initial elimination - over initial 12 hours
  • Slower later elimination - over 1-2 weeks

It is filtered freely at the glomerulus with reuptake of about 80% in the PCT.
Hyponatremia/sodium depletion can elevate lithium levels due to competition for reuptake in the kidney.

It is present in breast milk if breastfeeding.
There is some absorption in the bone and thyroid tissue.

Commencement

It is generally only started under expert psychiatric guidance.
Onset of action is relatively slow (1 to 2 weeks) and so additional alternative psychiatric treatment may be initially needed in extreme cases.

Some initial investigations are needed to aid safe initiation and monitoring:
  • U&Es - ensure adequate renal function
  • TFTs
  • Bone profile +/- Mg2+
  • ECG

Caution is needed regarding potential drug interaction.
These are essential any drugs that may interfere with the renal elimination:
  • NSAIDs
  • ACEi
  • Diuretics - particularly thiazides
It is teratogenic - use only in the 2nd/3rd trimester if essential.

Advice should be given regarding:
  • Avoiding stopping suddenly - can precipitate notable worsening of symptoms
  • Avoidance of interacting drugs
  • Awareness of signs of toxicity and side effects

Monitoring

There is some variation between laboratories.
The usual therapeutic range is 0.4-1.0 mmol/L.

The level should be taken at 12 hours post dose.
Monitoring needs to be undertaken:
  • Every 3 months
  • With intercurrent illness

Additional regular monitoring (6-12 months) should include:
  • U&Es
  • TFTs

Toxicity

This can occur with levels >1.5mmol/L
Serious toxicity can occur at levels >2mmol/L
It may also occur at ‘normal’ plasma levels, and so presence of symptoms should be viewed with suspicion.

Features of toxicity include:
  • GI disturbance
    • Nausea and vomiting
    • Diarrhoea
    • Anorexia
  • CNS disturbance
    • Drowsiness
    • Apathy
    • Restlessness
    • Dysarthria
    • Ataxia
    • Tremor
    • Twitching
    • Dizziness
  • Thirst
  • Polyuria

Severe toxicity may include:
  • Major CNS disturbance
    • Coma
    • Seizures
    • Hyperreflexia
  • Circulatory collapse
  • Renal failure
  • Hypokalaemia

ECG changes may include:
  • QRS widening
  • T wave flattening/inversion
  • SA/AV block

There are a number of side effects that may occur, even at therapeutic doses:
  • Abdominal pain
  • Nausea
  • Fine tremor
  • Metallic taste
  • Weight gain
  • Oedema
  • Hypothyroidism
  • Hyperparathyroidism
  • Nephrogenic DI

Management of toxicity

This should initially take a supportive approach (i.e. A to E).
  • Airway and breathing support may be needed for CNS depression
  • Benzodiazepines can be used to treat seizures

Haemodialysis is the definitive treatment of severe toxicity.

Anaesthetic Implications

Important effects include:
  • Prolongation of neuromuscular blockers
  • Potential augmentation of effects of general anaesthesia
  • Interaction with renally active drugs e.g. NSAIDs

It has been suggested that lithium be withheld for the 24 hours before surgery, but the risk of psychiatric deterioration with abrupt cessation is quite significant, meaning that the risk vs benefit balance may favour continuing it.

Links & References

  1. Rull, G. Lithium. Patient.info. 2016. https://patient.info/doctor/lithium
  2. Bromhead, H. Feeney, A. Anaesthesia and psychiatric drugs - part 2. ATOTW 175. 2010. https://www.aagbi.org/sites/default/files/175-Anaesthesia-and-psychiatric-drugs-part-2-Mood-stabilisers-and-antipsychotics.pdf
  3. Flood, S. Bodenham, A. Lithium: mimicry, mania and muscle relaxants. CEACCP. 2010. 10(3):77-80 https://academic.oup.com/bjaed/article/10/3/77/478472