UIC, Dept. of Psychiatry

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Pediatric Mood Disorders Clinic
Lithium Usage in Children

Lithium has been used as a mood stabilizer to treat children with bipolar disorder and impulse dyscontrol. It has been approved by the FDA for treatment in children 12 years and older, and few studies have been conducted on its effects in children of prepubertal age.

Pharmacokinetics

Absorption: within 6-8 hours; peak plasma levels within �-2 hours
Distribution: slow entry into intracellular compartment; no protein binding; some sequestration in bone
Metabolism: none
Elimination: via kidneys. T� = 24 hours. It is debatable whether or not children actually excrete Li faster than adults. The latest studies show that both children and adults eliminate Li at the same rate, and elimination is only impaired in the elderly.

Adverse Effects

Neuromuscular/CNS:

therapeutic � fine tremor, muscle hyperirritability
toxicity � ataxia, confusion, dysarthria, choreo-athetotic movements, hyperactive DTR, EPS including acute dystonia, seizures, coma, death

Cardiovascular:

arrhythmias, hypotension, bradycardia, sinus node dysfunction with sever bradycardia (which may result in syncope)

Gastrointestinal:

anorexia, nausea, vomiting, diarrhea, gastritis, abdominal pain

Genitourinary:

glycosuria, decreased creatinine clearance, albuminemia, oliguria, symptoms of nephrogenic diabetes insipidus including polyuria, thirst, polydipsia

Dermatologic:

drying and thinning of hair, alopecia, anesthesia of skin, acne, chronic folliculitis

Autonomic:

blurred vision, dry mouth, impotence/sexual dysfunction

Hematologic:

leukocytosis

Thyroid Abnormalities:

hypothyroidism

Dosing

A 1998 study conducted by Hagino et al compared the efficacy and side effect profile of two different dosing methods: weight-based dosing schedule (WBLE) vs. single-dose kinetics-based method (KBLE).

*The WBLE was based on an original 1986 study conducted by Weller et al that involved 15 children between the ages of 6 and 12. These hospitalized children received lithium at a starting does of 30mg/kg/day. It was found that mean serum Li levels during the first week of treatment fell within the presumed therapeutic range of 0.6-1.2 mEq/L. No side effects were reported in these children.

*The KBLE was described by Geller and Fetner in 1989, where they based their dosing on a nomogram derived from measurements of serum Li levels in 25 adults 24 hours after a single dose of 600 mg. Six children between the ages of 9 and 12 were administered 600 mg, and 24 hours later, based on their levels, they received doses of 600mg/day as projected by the nomogram. 7 day Li levels were 0.4-0.7 mEq/L, presumably also within the therapeutic range. No side effects were reported in these children.

The Hagino study took these results and treated eleven 4-6 year olds with Li either by KBLE or WBLE dosing. Neither of these dosing methods avoided side effects in children under six years of age. It concluded that WBLE should be used when the physician intends to achieve therapeutic levels acutely within a short period of time, such as a acute hospital setting. KBLE dosing can be adjusted gradually, and therefore has advantages for use in an outpatient setting.

A 1995 study also conducted by Hagino et al studied the side effect profile of chilren taking Li for two weeks between the ages of 4-6. Twenty children were studied, and the following results were reported:

40% experienced nuisance side effects- tremor, nausea, polyuria
20% experienced serious side effects- confusion, ataxia, dysarthria
Children who did and did not experience side effects were all within the therapeutic range of 0.6 � 1.2 mEq/L; the severity of the side effect did not correlate with the serum Li level
Side effects occurred within the first 1� weeks of treatment. No new side effects were seen after day 11.
Although Li treatment was suspended because of adverse effects, in these children it was later resumed without further untoward effects.

References:

Hagino, O MD; Weller, E MD; Weller, R MD; Fristad M, PhD. Comparison of Lithium Dosage Methods for Preschool- and Early School-Age Children. J of Am Acad of Child & Adolesc Psych, Jan 1998, 37(1):60-65.

Hagino, O MD et al. Untoward Effects of Lithium Treatment in Children Aged Four through Six Years. J of Am Acad of Child & Adolesc Psych, Dec 1995, 34(12):1584-1590.

MD Consult