Robert L Findling1, Adelaide Robb2, Nora K McNamara3, Mani N Pavuluri4, Vivian Kafantaris5, Russell Scheffer6, Jean A Frazier7, Moira Rynn8, Melissa DelBello9, Robert A Kowatch10, Brieana M Rowles11, Jacqui Lingler3, Karen Martz12, Ravinder Anand12, Traci E Clemons12, Perdita Taylor-Zapata13. 1. The Johns Hopkins University/Kennedy Krieger Institute, Baltimore, Maryland; rfindli1@jhmi.edu. 2. Children's National Medical Center, George Washington University, Washington District of Columbia; 3. Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio; 4. Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois; 5. The Zucker Hillside Hospital and Feinstein Institute for Medical Research of the North Shore-Long Island Jewish Health System, Manhasset, New York; 6. University of Kansas School of Medicine, Wichita, Kansas; 7. Department of Psychiatry, University of Massachusetts Medical School/UMASS Memorial Medical Center, Worcester, Massachusetts; 8. New York State Psychiatric Institute/Columbia University, New York, New York; 9. University of Cincinnati College of Medicine, Cincinnati, Ohio; 10. Wexner Medical Center/Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio; 11. UPMC CancerCenter, Pittsburgh, Pennsylvania; 12. The EMMES Corporation, Rockville, Maryland; and. 13. Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Abstract
BACKGROUND:Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolarI disorder (BP-I) are lacking. METHODS: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versusplacebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis. RESULTS: The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression-Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (-0.1 ± 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain. CONCLUSIONS:Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.
RCT Entities:
BACKGROUND:Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking. METHODS: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis. RESULTS: The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression-Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (-0.1 ± 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain. CONCLUSIONS:Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.
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