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Lithium is an alkali metal that is administered as a monovalent cation (Li+) for the treatment of bipolar disorder. In the United States, orally administered carbonate and citrate salts of lithium are available. While lithium is still used as a primary mood stabilizer for bipolar disorders, valproic acid, carbamazepine, or lamotrigine are also reasonable choices.1,2 Although this drug has been used in psychiatric medicine since the 1940s, the mechanism of action of lithium is largely unknown. Among the current theories are competition with other cations at receptor and tissue sites, dopamine-receptor supersensitivity blockage, decreased stimulation of β-receptor–induced adenylate cyclase, and enhanced sensitivity to serotonin (5-HT), acetylcholine, and γ-aminobutyric acid (GABA).1,2


The general therapeutic range for lithium is 0.6-1.5 mmol/L. Because lithium is a monovalent cation, the therapeutic range expressed in mEq/L is identical to these values (ie, 0.6-1.5 mEq/L). However, most clinicians apply different therapeutic concentration ranges depending on the clinical situation of the patient.3,4 For individuals with acute mania, a minimum lithium concentration of 0.8 mmol/L is usually recommended. The usual desired range for these individuals is 0.8-1 mmol/L. If patients with acute mania do not respond to these levels, it is necessary to occasionally use lithium concentrations of 1-1.2 mmol/L and in some instances concentrations as high as 1.2-1.5 mmol/L are needed. For long-term maintenance use, the usual desired range is 0.6-0.8 mmol/L. If patients do not respond to these levels during maintenance treatment, occasional use of lithium concentrations equal to 0.9-1 mmol/L is required and in some cases concentrations as high as 1-1.2 mmol/L are necessary to gain an adequate outcome.

These therapeutic ranges are based on steady-state lithium serum concentrations obtained 12 hours after a dose. The adoption of a standardized 12-hour postdose lithium concentration to assess dose and response has been paramount in establishing the aforementioned therapeutic ranges for the agent.5 After oral administration, lithium concentrations follow a complex concentration-time curve that is best described using multicompartment models (Figure 21-1).5,6,7,8, and 9 There is a great deal of variability among patients in the time needed for distribution between serum and tissues to occur, and under these conditions using a uniform time for the determination of steady-state serum concentrations is important. When lithium serum concentration monitoring is anticipated for an individual, the patient needs to understand that it is important to take their medication as instructed for 2-3 days before the blood sample is obtained, to have the blood sample withdrawn 12 ± 0.5 h after the last dose, and to report any discrepancies in compliance and blood sampling time to their care provider.


Lithium ion serum concentration-time curve after a single 900-mg oral dose of lithium carbonate (24.4 mmol or mEq of lithium ion) rapid-release ...

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