Lithium

Overview:

Lithium as lithium carbonate is used as a psychoactive agent in the treatment of manic depressive disorders. Lithium therapy demands daily monitoring of serum lithium levels until the proper dose schedule is determined. Serum elimination half-life ranges from 20 to 60 hours. Insomnia in a low-range group is described. Tremor, gastrointestinal symptoms, urinary frequency, and weight gain were less frequent at lower levels.1 Intoxication never occurs suddenly. Several days to a week before full-blown symptoms develop, a patient will experience lethargy, drowsiness, tremor, muscle twitching, dysarthria, anorexia and vomiting or diarrhea. A fully developed case of intoxication shows coma to semicoma, rigidity, hyperactive reflexes and seizures at times. There is a high incidence of pulmonary complications. It is advisable to perform periodic plasma sodium determinations. Low plasma sodium levels are associated with lithium retention; high levels with lithium elimination. Varying degrees of nephrogenic diabetes insipidus have been reported to occur in 33% of lithium treated patients. Lithium significantly inhibits antidiuretic hormone induced water transport in kidney. Lithium interferes with solute and water absorption from the gastrointestinal system producing nausea, vomiting, diarrhea, and abdominal pain. These symptoms may occur at any time, at any serum level. They most commonly occur during early treatment stages and usually clear spontaneously or by adjustment of dosage. Chronic lithium administration has a goitrogenic effect on 4% of lithium treated patients, with or without hypothyroidism. In general, lithium administration results in slightly decreased serum T4 levels and transiently elevated levels of TSH in nearly 33% of these patients.

Lithium affects the cardiac conduction system by incomplete substitution for other cations, especially sodium and potassium. These electrolyte changes account for the usually unimportant and reversible T-wave depressions observed in 10% to 20% of patients on lithium therapy.

Lithium is completely absorbed six to eight hours after oral administration. Since the onset of action is slow (5 to 10 days), parenteral administration is of no advantage. The plasma half-life is 17 to 36 hours, and this drug is eliminated almost entirely by the kidneys. Lithium clearance averages approximately 20% of creatinine clearance, but significant variability exists among patients.

Lithium ion is not protein bound, is distributed in total body water, and is concentrated in various tissues to different degrees. After a steady-state has been achieved, the lithium level in cerebrospinal fluid is about 40% of that in serum, and renal clearance for an individual remains relatively constant.

In general, a good correlation exists between the serum concentration of lithium ion and therapeutic efficacy and toxicity; however, some patients who show no therapeutic benefit have adequate serum concentrations of lithium but low erythrocyte concentrations. Since lithium works intracellularly, the erythrocyte concentration of the drug may be more relevant than levels in serum; therefore, in unresponsive patients, doses that produce higher than usual serum concentrations can be used if erythrocyte concentrations are lower.

1. Gelenberg AJ, Kane JM, Keller MB, et al. Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder. N Engl J Med. 1989 Nov 30; 321(22):1489-1493. PubMed 2811970

American Medical Association, Division of Drugs and Toxicology. Drug Evaluations Subscription. Chicago, Ill: AMA, Spring 1992.