title: Dosing strategies for lithium monotherapy in children and adolescents with bipolar I disorder.
abstract: 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.
authors.affiliation: Child and Adolescent Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. robert.findling@uhhospitals.org
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Vivian
authors.initials: V
authors.lastname: Kafantaris
authors.forename: Mani
authors.initials: M
authors.lastname: Pavuluri
authors.forename: Nora K
authors.initials: NK
authors.lastname: McNamara
authors.forename: Jon
authors.initials: J
authors.lastname: McClellan
authors.forename: Jean A
authors.initials: JA
authors.lastname: Frazier
authors.forename: Linmarie
authors.initials: L
authors.lastname: Sikich
authors.forename: Robert
authors.initials: R
authors.lastname: Kowatch
authors.forename: Jacqui
authors.initials: J
authors.lastname: Lingler
authors.forename: Jon
authors.initials: J
authors.lastname: Faber
authors.forename: Brieana M
authors.initials: BM
authors.lastname: Rowles
authors.forename: Traci E
authors.initials: TE
authors.lastname: Clemons
authors.forename: Perdita
authors.initials: P
authors.lastname: Taylor-Zapata
mesh_terms: D000293:Adolescent; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D001835:Body Weight; D002648:Child; D004305:Dose-Response Relationship, Drug; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D016651:Lithium Carbonate