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Dosing Strategies for Lithium Monotherapy in Children and Adolescents with Bipolar I Disorder


Journal Article

Findling, R.; Kafantaris, V.; Pavuluri, M.; McNamara, N.; McClellan, J.; Frazier, J.; Sikich, L.; Kowatch, R.; Lingler, J.; Faber, J.; Rowles, B.; Clemons, T.; Taylor-Zapata, P.

J Child Adolesc Psychopharmacol




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 /=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.

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