• Introduction & Key Points
• Indications for Lithium
• Dosage and administration
• Averse effects of lithium
• Pharmacokinetics and serum concerntrations
• Baseline tests and monitoring
• Drug interactions
• Continuation and maintenance treatment
• Cautions and contraindications to lithium treatment
• Cases
• References
• Issue 3 Contents

Pharmacokinetics and serum concentrations

Lithium is excreted unchanged and partially reabsorbed by the kidney. The half-life is approximately 24 hours (longer in renal impairment) which means that steady state drug concentrations are reached four to five days after initiation or a change in dose. Changes in renal function, fluid and electrolyte balance and interacting drugs can alter drug concentrations as can irregular dosing, poor compliance and missed doses. These factors need to be considered as an explanation for poor therapeutic response or toxicity.

Serum Level Monitoring

Lithium serum levels should be taken 10-14 hours post-dose.

Lithium serum levels should be measured:

• If there are signs of lithium toxicity (see below)
• Five days after initiation or change in dose, change in brand, change in dosage regimen (e.g. twice daily to once daily) or change to potentially interacting medication
• Weekly during acute treatment
• Every three months once patient’s mental state and lithium serum level are stable

Therapeutic range

For acute episodes a concentration towards the upper end of the range may be required (0.8-1.2 mmol/L). Some evidence suggests that the minimum therapeutic serum lithium level for acute mania is around 1.0 mmol/L. When a patient is acutely manic, lower serum levels may be seen than when the patient is euthymic despite the same dose of lithium. If the lithium dose is increased to treat the acute episode, it is essential to monitor the patient for clinical signs of toxicity. Repeat the lithium serum levels at least weekly as the episode resolves as the patient’s lithium serum level may rise.

Once the acute episode is resolved the lithium dose can usually be adjusted downwards to achieve a maintenance lithium serum level of between 0.6-0.8 mmol/L.¹ Serum levels lower than this are only warranted if the patient has had unacceptable adverse effects or has a history of maintenance of lower serum levels without relapse.

Signs of lithium toxicity

Toxicity generally occurs at concentrations > 1.5-2.0 mmol/L, but may do so at concentrations within the therapeutic range, especially in elderly people. Concentrations > 3.5 mmol/L are potentially fatal and haemodialysis is recommended.¹
Signs of lithium toxicity include; blurred vision, GI disturbances (increasing anorexia, nausea, vomiting and diarrhoea), muscle weakness, coarse tremor, lack of co-ordination, ataxia, dysarthria, drowsiness, sluggishness, confusion and convulsions.

Development of any of these signs necessitates an urgent lithium serum level. This should still be done 10-14 hours after the last dose, however the next dose should be withheld until the lithium serum level has been checked and the dosage adjusted as necessary.

Interpretation of serum lithium concentrations

The therapeutic range is simply a guide and there will be occasional patients who are controlled on concentrations outside the accepted range. It is important to assess individual patient response and signs of toxicity in conjunction with the serum concentration. A person on long term lithium may have an individual ‘lithium history’ indicating the serum concentrations normally associated with clinical response or dose related side effects for that individual.

The sampling time should be standardised at 10-14 hours after the last dose and should be consistent for each person. Interpretation is unreliable if sampling times are variable. If it is uncertain if a patient is compliant, reinforce the need for this and re-check the concentration after five days to ensure a reliable steady state result.

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Interpretation of serum lithium concentrations

Interpretation and action (Adapted from Lothian Guidelines)⁸

The concentration is low (e.g. < 0.6 mmol/L)

• If the person is well and the concentration is consistently low, but the norm for that individual, a dose alteration is not required.
• If the patient is unwell and a series of concentrations have been bordering on the lower end of the range:
  • Assess compliance
  • Re-check concentration after five days
  • Increase dose if appropriate

If the concentration is within the therapeutic range (e.g. 0.6-0.8 mmol/L)

• If the person is well and tolerating no action is required.
• If the person is well but complains of dose related side effects:
  • Investigate and exclude possible reasons for increased lithium concentrations, especially if these are higher than the norm for the individual.
  • If appropriate try a small dose reduction with assessment of clinical response.
• If the person is unwell increase the dose to within the acute treatment range (0.8-1.2 mmol/L). Liaise with a specialist if there is no response or adverse effects develop.

If the concentration is high (typically > 1.0 mmol/L), but with no signs of toxicity)

• Investigate possible explanations for high concentration. Correct where possible and re-check the concentration.
• If the concentration is one of several which have bordered on being too high encourage fluids, re-check level after five days and consider a dose decrease.
• If there is no clear explanation for the high concentration re-check and investigate renal function.
• N.B. Some people may need a relatively high concentration for control. Does the ‘lithium history’ indicate a reduced response if concentrations are lower? Extra vigilance for toxicity is required.