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.
Bipolar disorder - prophylaxis of
Mania/hypomania - acute management
Depression - prophylaxis
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.
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.
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
Bone profile +/- Mg2+
Caution is needed regarding potential drug interaction. These are essential any drugs that may interfere with the renal elimination:
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
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:
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:
Nausea and vomiting
Severe toxicity may include:
Major CNS disturbance
ECG changes may include:
T wave flattening/inversion
There are a number of side effects that may occur, even at therapeutic doses:
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.
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.