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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 treatment for bipolar disorders, valproic acid,
lamotrigine, or carbamazepine may be used for some subsets of the
disease.1 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
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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 (i.e.,
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.
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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
17-1).5–9 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 hours after the last dose, and to report
any discrepancies in compliance and blood sampling time to their
care provider.
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