Lithium carbonate is a white, light, alkaline powder with molecular formula LiCO and molecular weight 73.89. Lithium is an element of the alkali-metal group with atomic number 3, atomic weight 6.94, and an emission line at 671 nm on the flame photometer.
Inert ingredients are: Blue 1 Lake; dibasic calcium phosphate; magnesium stearate; polyethylene glycol; sodium lauryl sulfate; starch; Yellow 5 Lake.
Lithium should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, and to patients receiving diuretics, since the risk of lithium toxicity is very high in such patients. If the psychiatric indication is life-threatening, and if such a patient fails to respond to other measures, lithium treatment may be undertaken with extreme caution, including daily serum lithium determinations and adjustment to the usually low doses ordinarily tolerated by these individuals. In such instances, hospitalization is a necessity.
Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued.
Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy. Morphologic changes have also been seen in manic-depressive patients never exposed to lithium. The relationship between renal functional and morphologic changes and their association with lithium therapy have not been established.
When kidney function is assessed, for baseline data prior to starting lithium therapy or thereafter, routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24 hour urine volume) and glomerular function (e.g., serum creatinine or creatinine clearance). During lithium therapy, progressive or sudden changes in renal function, even within the normal range, indicate the need for reevaluation of treatment.
Lithium therapy has been reported in some cases to be associated with morphologic changes in the kidneys. The relationship between such changes and renal function has not been established.
An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol. A causal relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. The possibility of similar adverse interactions with other antipsychotic medication exists.
Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels (see ).
Outpatients and their families should be warned that the patient must discontinue lithium carbonate therapy and contact his physician if such clinical signs of lithium toxicity as diarrhea, vomiting, tremor, mild ataxia, drowsiness, or muscular weakness occur.
Lithium carbonate may impair mental and/or physical abilities. Caution patients about activities requiring alertness (e.g., operating vehicles or machinery).
Lithium may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking agents should be given with caution to patients receiving lithium.
Adverse reactions are seldom encountered at serum lithium levels below 1.5 mEq./l., except in the occasional patient sensitive to lithium. Mild to moderate toxic reactions may occur at levels from 1.5–2.5 mEq./l., and moderate to severe reactions may be seen at levels from 2.0–2.5 mEq./l., depending upon individual response to the drug.
Fine hand tremor, polyuria, and mild thirst may occur during initial therapy for the acute manic phase, and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of lithium administration.
These side effects are an inconvenience rather than a disabling condition, and usually subside with continued treatment or a temporary reduction or cessation of dosage. If persistent, a cessation of dosage is indicated.
Diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination may be early signs of lithium intoxication, and can occur at lithium levels below 2.0 mEq./l. At higher levels, giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine may be seen. Serum lithium levels above 3.0 mEq./l. may produce a complex clinical picture involving multiple organs and organ systems. Serum lithium levels should not be permitted to exceed 2.0 mEq./l. during the acute treatment phase.
The following reactions have been reported and appear to be related to serum lithium levels, including levels within the therapeutic range:
The desirable lithium levels are 0.6 to 1.2 mEq./l. Dosage will vary from one individual to another, but usually 300 mg t.i.d. or q.i.d will maintain this level. Serum lithium levels in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months.
Patients abnormally sensitive to lithium may exhibit toxic signs at serum levels of 1.0 to 1.5 mEq./l. Elderly patients often respond to reduced dosage, and may exhibit signs of toxicity at serum levels ordinarily tolerated by other patients.
