@article{a308ff27bc384d72bd8a2f7d70c6d8c0,
title = "Lithium for the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Discontinuation Study",
abstract = "Objective: This study examined the role of lithium in the maintenance treatment of pediatric patients with bipolar I disorder (BP-I). Method: Participants aged 7 to 17 years who presented with a manic or mixed episode received 24 weeks of lithium treatment in one of two multiphase studies, the Collaborative Lithium Trials (CoLT 1 and CoLT 2). Responders were randomized to continue lithium or to be cross-titrated to placebo for up to 28 weeks. The primary outcome measure was relative risk of study discontinuation for any reason. Results: A Cox regression analysis found that those who continued treatment with lithium (n = 17) had a lower hazard ratio compared to those who received placebo (n = 14) (p =.015)]. The vast majority of discontinuations were due to mood symptom exacerbations, with most of these occurring in the placebo-treated group. Discontinuation for other reasons occurred at similarly low rates across both group. Most adverse events were mild to moderate in severity, and only one study participant was discontinued from the trial owing to a serious adverse event (aggression). There was no statistically significant difference with respect to weight gain in participants receiving lithium compared to those receiving placebo. Conclusion: This randomized, double-blind, placebo-controlled Discontinuation Trial builds support for the role of lithium as a maintenance treatment in pediatric patients with bipolar disorder and for the safety and tolerability of 28 weeks of maintenance lithium treatment. Clinical trial registration information: Lithium for the Treatment of Pediatric Mania; https://clinicaltrials.gov/; NCT00442039 (CoLT 1). Safety and Efficacy Study of Lithium for the Treatment of Pediatric Mania; https://clinicaltrials.gov/; NCT01166425 (CoLT 2).",
keywords = "bipolar, children, lithium, treatment",
author = "Findling, {Robert L.} and McNamara, {Nora K.} and Mani Pavuluri and Frazier, {Jean A.} and Moira Rynn and Russell Scheffer and Vivian Kafantaris and Adelaide Robb and Melissa DelBello and Kowatch, {Robert A.} and Rowles, {Brieana M.} and Jacqui Lingler and Jian Zhao and Traci Clemons and Karen Martz and Ravinder Anand and Perdita Taylor-Zapata",
note = "Funding Information: This work was sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) “Best Pharmaceuticals for Children Act Pediatric Off-Patent Drug Study (PODS): Lithium in the Treatment of Pediatric Mania” (contract HHSN275200503406C).Disclosure: Dr. Findling has received research support, acted as a consultant, and/or served on a speaker's bureau for Aevi, Akili, Alcobra, Amerex, the American Academy of Child and Adolescent Psychiatry (AACAP), American Psychiatric Press, Bracket, Epharma Solutions, Forest, Genentech, Ironshore, KemPharm, Lundbeck, the National Institutes of Health (NIH), Neurim, Nuvelution, Otsuka, the Patient-Centered Outcomes Research Institute (PCORI), Pfizer, Physicians Postgraduate Press, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, Syneurx, Teva, Tris, TouchPoint, and Validus. Dr. McNamara has received research or travel support from and/or acted a consultant for Acadia Pharmaceuticals, F. Hoffmann-La Roche AG, Forest, Janssen Pharmaceuticals, Lundbeck, NaBen, NIH, Otsuka Pharmaceuticals, Pfizer Inc., Shire, Sunovion Pharmaceuticals, and Tonix Pharmaceuticals. Dr. Pavuluri is the cofounder of the Brain and Wellness Institute and holds shares in Medcircle, Inc. Dr. Frazier has received grant or research support from NIH, the National Institute of Mental Health (NIMH), Fulcrum Therapeutics, Janssen Research and Development, LLC, Neuren Pharmaceuticals, Roche, and SyneuRX International. She has served on the editorial board of the Harvard Review of Psychiatry and as associate editor of the Journal of Child and Adolescent Psychopharmacology. Dr. Rynn has received grant or research support from NIMH, NICHD, Neurocrine Biosciences, Inc., and Pfizer Inc. She has received royalties from UptoDate. Dr. Robb has received research and/or travel support, has received royalties and/or honoraria, has stock or equity in, acted as a consultant, and/or served on a speaker's bureau for Actavis/Allergan/Forest, Aevi Genomic Medicine, AACAP, American Academy of Pediatrics, Bracket, the Child and Adolescent Psychiatric Society of Greater Washington local branch, Case Western Reserve University, College of Neurologic and Psychiatric Pharmacists, Eli Lilly and Co., GlaxoSmithKline, Guilford Press, Janssen Pharmaceuticals, Inc., Lundbeck, the National Center for Advancing Translational Sciences, Neuronetics, Neuroscience Education Institute, NICHD, NIMH, the National Institute of Neurological Disorders and Stroke, the North American Center for Continuing Medical Education, Otsuka, Pfizer Inc., Shire, Sunovion Pharmaceuticals, Supernus, SyneuRx, and the University of Cambridge. She has also participated in paid speaking engagements at the University of Kansas Medical Center, Our Lady of the Lake Hospital, and the Carle University School of Medicine. Dr. DelBello has received grant or research support from NIMH, the National Institute of Diabetes and Digestive and Kidney Diseases, PCORI, Amarex, Johnson and Johnson, Supernus, Sunovion, Otsuka, Pfizer, Lundbeck, and Shire. She has served as a consultant to, on the advisory boards of, and/or received honoraria from Akili Interactive, CMEology, Johnson and Johnson, Lundbeck, Neuronetics, Pfizer, Sunovion, Supernus, and Takeda. She has served as field editor of Bipolar Disorders and associate editor of the Journal of Child and Adolescent Psychopharmacology. Dr. Kowatch has served on a Data Safety Monitoring Board for Forest and Pfizer Inc. Drs. Scheffer, Kafantaris, Zhao, Clemons, Anand, and Taylor-Zapata, Ms. Rowles, Mr. Lingler, and Ms. Martz report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) “Best Pharmaceuticals for Children Act Pediatric Off-Patent Drug Study (PODS): Lithium in the Treatment of Pediatric Mania” (Contract HHSN275200503406C). Funding Information: This work was sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) “Best Pharmaceuticals for Children Act Pediatric Off-Patent Drug Study (PODS): Lithium in the Treatment of Pediatric Mania” (contract HHSN275200503406C). Publisher Copyright: {\textcopyright} 2018 American Academy of Child and Adolescent Psychiatry",
year = "2019",
month = feb,
doi = "10.1016/j.jaac.2018.07.901",
language = "English (US)",
volume = "58",
pages = "287--296.e4",
journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
issn = "0890-8567",
publisher = "Elsevier Limited",
number = "2",
}