Serum lithium monitoring of prophylactic treatment. Critical review and updated recommendations.

Abstract

Lithium treatment of mania was the first psychiatric therapy to be monitored through determination of blood concentrations of the drug; the procedure served to guard against overdosage and poisoning. When lithium became employed prophylactically against manic and depressive recurrences, monitoring was used to ensure an adequate drug plasma concentration; no symptoms were present during the intervals between affective episodes, and dosage adjustment could therefore not be based on clinical observation. The pharmacokinetic properties oflithium have been studied extensively (Amidsen 1977; Cooper 1987; Lehmann 1986; Schou 1957, 1983a). The lithium ion is absorbed readily from the gastrointestinal tract; it is not bound to plasma proteins; it penetrates into tissues at varying rates; and its apparent volume of distribution corresponds to about 70% of bodyweight. Elimination takes place almost exclusively through the kidneys, with a half-life of 15 to 30 hours. Lithium clearance is about one-quarter of the glomerular filtration rate and falls when the latter falls, for example during kidney disease. It may also fall independently of the glomerular filtration rate, namely during dehydration and sodium depletion. After each intake of a lithium salt, the serum lithium concentration rises and reaches a peak after 2 to 4 hours (6 to 8 hours with delayed release formulations); this is followed by a gradual and largely exponential fall until the next intake. Blood samples for serum lithium determination should be drawn a fixed time interval after the last intake of lithium, usually in the morning 10 to 12 hours after the evening dose. All this is well known, and determination of the serum lithium concentration at regular intervals during treatment has for a long time been considered mandatory for safe and responsible therapy. But is that practice still justified? Is serum monitoring under all circumstances strictly necessary? What do determinations during the treatment protect the patients against? Can serum lithium monitoring be employed more rationally as a means of ensuring safe and effective treatment? The present review attempts to answer these questions.