Lithium is used in the prophylaxis of bipolar and unipolar affective
disorders and in the treatment of acute mania
Monitoring serum lithium concentrations is an important part of treatment in patients with affective disorders as the drug's toxic: therapeutic ratio is very low and its pharmacokinetics vary from person to person, making accurate prediction of dosage difficult. The variation is due to differences in absorption, distribution, and elimination.
Serum (prepared from clotted blood) and plasma (prepared from
anticoagulated blood) can be used interchangeably for other drug
measurements. However, serum is usually used for measurement for lithium
to avoid potential interference from lithium heparin, which is used as
Absorption of lithium is highly variable, depending on the formulation used. The rate and extent of absorption varies between modified release and conventional formulations, but there is also variability from one modified release formulation to another.
The variations in the clearance and apparent volume of distribution of lithium result in variation in its half life from 7 hours to 41 hours.
In this chapter we apply to lithium the criteria which must be fulfilled in part or in full before measurement of its plasma concentration can be considered worth while.
Criteria for measurement
Is there difficulty in interpreting clinical evidence of the therapeutic or toxic effects?
Although it may be possible to achieve a steady state serum lithium concentration within the therapeutic range relatively rapidly (for example, by giving a loading dose), the onset of a detectable therapeutic action in patients with acute mania may be delayed for up to two weeks.
Even when a therapeutic effect has occurred it may be difficult to know whether the effect is optimal and whether it is attributable to the drug or to spontaneous remission. Furthermore, assessment of the extent to which lithium is contributing to a change in mood may be difficult in patients taking other mood altering drugs, as is commonly the case.
Furthermore, lithium is used for prophylaxis in patients with recurrent unipolar and bipolar affective illnesses. In such cases although a relapse may be evidence of a lack of therapeutic effect, you cannot be sure that the prophylactic dose is optimal in patients who remain in remission. In addition, such patients may well experience mild adverse effects of lithium, which occur commonly with therapeutic dosages. It may therefore be difficult to find a dosage that is effective and does not cause adverse effects.
Is there a good relation between the serum concentration and its therapeutic or toxic effects?
Because serum lithium concentrations vary quite widely between doses it is important that they are measured at a standard time. We will call this measurement the standard serum lithium concentration.
Interpretation of the results of studies of the relation between serum concentrations of lithium and its therapeutic effect has been made difficult by the fact that in many such studies measurement of serum lithium concentration has not been made at the same standard time after the previous dose. Despite this there is some evidence that a therapeutic effect is most likely to be achieved in patients with acute mania if the standard serum lithium concentration is above 0.8 mmol/l.
There is also evidence that there is little benefit to be gained by increasing the concentration above 1.2 mmol/l and that the risk of adverse effects increases considerably above this concentration. Thus a reasonable therapeutic range for steady state standard serum lithium concentrations in patients with acute mania is
The therapeutic range for steady state standard serum lithium
concentrations in the treatment of acute mania is 0.8-1.2 mmol/l