Dosing strategies for lithium monotherapy in children and adolescents with bipolar I disorder.

Publication Type
Journal Article
Year of Publication
Findling, Robert L; Kafantaris, Vivian; Pavuluri, Mani; McNamara, Nora K; McClellan, Jon; Frazier, Jean A; Sikich, Linmarie; Kowatch, Robert; Lingler, Jacqui; Faber, Jon; Rowles, Brieana M; Clemons, Traci E; Taylor-Zapata, Perdita
J Child Adolesc Psychopharmacol
Date Published
2011 Jun
Adolescent; Antimanic Agents; Bipolar Disorder; Body Weight; Child; Dose-Response Relationship, Drug; Evidence-Based Medicine; Female; Humans; Lithium Carbonate; Male; Severity of Illness Index; Treatment Outcome

OBJECTIVE: The primary goal of this exploratory study was to obtain data that could lead to evidence-based dosing strategies for lithium in children and adolescents suffering from bipolar I disorder.

METHODS: Outpatients aged 7-17 years meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic criteria for bipolar I disorder (manic or mixed) were eligible for 8 weeks of open label treatment with lithium in one of three dosing arms. In Arm I, participants began treatment at a dose of 300 mg of lithium twice daily. The starting dose of lithium in Arms II and III was 300 mg thrice daily. Patients in Arms I and II could have their dose increased by 300 mg/day, depending on clinical response, at weekly visits. Patients in Arm III also had mid-week telephone interviews after which they could also have their dose of lithium increased by 300 mg per day. Youths weighing <30 kg were automatically assigned to Arm I, whereas youths weighing ≥30 kg were randomly assigned to Arm I, II, or III. Randomization was balanced by age (7-11 years, 12-17 years) and sex in approximately equal numbers. A priori response criteria were defined as a Clinical Global Impressions-Improvement scale score of ≤ 2 and a 50% decrease from baseline on the Young Mania Rating Scale.

RESULTS: Of the 61 youths [32 males (52.5%)] who received open-label lithium, 60 youths completed at least 1 week of treatment and returned for a postbaseline assessment. Most patients had a ≥ 50% improvement in Young Mania Rating Scale score, and more than half of the patients (58%) achieved response. Overall, lithium was well tolerated. All three treatment arms had similar effectiveness, side effect profiles, and tolerability of lithium.

CONCLUSIONS: On the basis of these results, a dosing strategy in which pediatric patients begin lithium at a dose of 300 mg thrice daily (with an additional 300 mg increase during the first week), followed by 300 mg weekly increases until a priori stopping criteria are met, will be used in an upcoming randomized, placebo-controlled trial.