@article{ce57f5a8cae249cbaf8df5b7fa07b691,
title = "Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment",
abstract = "Objective The Treatment of Early Age Mania (TEAM) study evaluated lithium, risperidone, and divalproex sodium (divalproex) in children with bipolar I disorder who were naive to antimanic medication, or were partial or nonresponders to 1 of 3 study medications. This report evaluates the benefit of either an add-on or a switch of antimanic medications for an 8-week trial period in partial responders and nonresponders, respectively. Method TEAM is a randomized, controlled trial of individuals (N = 379) aged 6 to 15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (mixed or manic phase). Participants (n = 154) in this report were either nonresponders or partial responders to 1 of the 3 study medications. Nonresponders (n = 89) were randomly assigned to 1 of the other 2 antimanic medications and cross-tapered. Partial responders (n = 65) were randomly assigned to 1 of 2 other antimanic medications as an add-on to their initial medication. Adverse event (AE) rates are reported only for the add-on group. Results Response rate for children switched to risperidone (47.6\%) was higher than for those switched to either lithium (12.8\%; p =.005; number needed to treat [NNT] = 3; 95\% CI = 1.71-9.09) or divalproex (17.2\%; p =.03; NNT = 3; 95\% CI = 1.79-20.10); response rate for partial responders who added risperidone (53.3\%) was higher than for those who added divalproex (0\%; p =.0002; NNT = 2; 95\% CI = 1.27-3.56) and trended higher for lithium (26.7\%; p =.07; NNT = 4). Reported AEs in the add-on group were largely consistent with the known AE profile for the second medication. Weight gain (kg) was observed for all add-on medications: lithium add-on (n = 29 of 30) = 1.66 ± 1.97; risperidone add-on (n = 15 of 15) = 2.8 ± 1.34; divalproex add-on (n = 19 of 20) = 1.42 ± 1.96. There was no evidence at the 5\% significance level that the average weight gain was different by study medication for partial responders (p =.07, 1-way analysis of variance). Conclusion Risperidone appears to be more useful than lithium or divalproex for children with bipolar I disorder and other comorbid conditions who are nonresponders or partial responders to an initial antimanic medication trial.",
keywords = "bipolar, mania, nonresponders, pharmacology, treatment",
author = "Walkup, \{John T.\} and Wagner, \{Karen Dineen\} and Leslie Miller and Gayane Yenokyan and Luby, \{Joan L.\} and Joshi, \{Paramjit T.\} and Axelson, \{David A.\} and Adelaide Robb and Salpekar, \{Jay A.\} and Dwight Wolf and Abanti Sanyal and Boris Birmaher and Benedetto Vitiello and Riddle, \{Mark A.\}",
note = "Funding Information: The study was funded by the National Institute of Mental Health and involved 6 academic child and adolescent psychiatry centers: Children{\textquoteright}s National Medical Center, Johns Hopkins University (performance and data analysis site), University of Pittsburgh, University of Texas at Galveston and at Southwestern Medical Center in Dallas, and Washington University (performance and coordinating site). Informed consent was obtained from primary caretakers, and assent was obtained from children. Each site{\textquoteright}s human studies committee approved the protocol, and the National Institute of Mental Health Data and Safety Monitoring Board monitored study conduct. Abbott Laboratories supplied Depakote-brand valproate (divalproex sodium) for the study but had no other input in the study design, implementation, data analysis, or interpretation or manuscript preparation. Funding Information: This study received funding from NIMH cooperative agreement grants U01 MH064846 (Geller/WU), U01 MH064850 (Wagner/UTMB), U01 MH064851 (Axelson/Pitt), U01 MH064868 (Luby/WU), U01 MH064869 (Walkup/JHU), U01 MH064887 (Joshi/CNMC), and U01 MH064911 (discontinued site/reallocated). Partial support for statistical work was also received from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH; 1UL1TR001079). Dr. Yenokyan served as the statistical expert for this research. The authors gratefully acknowledge the pivotal contributions of Barbara Geller, MD, of Washington University, in designing and overseeing this project fromits inception through to its publication. The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, NIH, or NIMH. Dr. Walkup has received free drug/placebo from the following pharmaceutical companies for NIMH-funded studies: Eli Lilly and Co. (2003), Pfizer (2007), and Abbott (2005). He was paid for a one-time consultation with Shire (2011). He is a paid speaker for the Tourette Syndrome-Center for DiseaseControl and Prevention outreach educational programs, the American Academy of Child and Adolescent Psychiatry (AACAP), and the American Psychiatric Association. He has received royalties for books on Tourette syndrome from Guilford Press and Oxford University Press. He has received grant funding from the Hartwell Foundation and the Tourette Syndrome Association. He is an unpaid advisor to the Anxiety Disorders Association of America, Consumer Reports, and the Trichotillomania Learning Center. Dr. Wagner has received honoraria from UBM Medica, the Las Vegas Psychiatric Society, AACAP, Partners Healthcare, Weill Cornell Medical School, and the Nevada Psychiatric Association. Dr. Miller has received grant funding from NIMH and has received proceeds from the sale of Merck and Co., Inc. stock. Dr. Luby has received grant or research support from NIMH. She has received royalties from Guilford Press. Dr. Joshi holds leadership positions as president of AACAP for the term 2013-2015 and as a psychiatry director of the American Board of Psychiatry andNeurology (ABPN). Dr. Axelson has served as a consultant for Janssen Research and Development and has received royalties fromWolters Kluwer. Dr. Robb has received research support from, acted as a consultant to, and/or served on a speaker''s bureau of AACAP, the American Academy of Pediatrics, Bracket, Bristol-Myers Squibb, Eli Lilly and Co., Actavis/ Allergan/Forest Laboratories, GlaxoSmithKline, Ironshore, Janssen, Johnson and Johnson, Lundbeck, Merck, the National Institute of Child Health and Human Development, the National Institute of Neurologic Diseases and Stroke, Neuronetics, Otsuka, Pfizer, PICORI, Roche, Rhodes, SyneuRx, Sunovion, Supernus, and Takeda. She holds stock in IRAs in Eli Lilly and Co., GlaxoSmithKline, Johnson and Johnson and Pfizer. Dr. Salpekar has served as a member of a Data and Safety Monitoring Board for studies sponsored by the NIMH Intramural Program. He has received honoraria from the Gulf ChildMental and Behavioral Health Society and has served as a consultant for Sunovion. Dr. Wolf has received direct salary support from theMayo Clinic. Dr. Birmaher has received funding from NIMH and royalties for books from UpToDate, APA Press, and Random House, Inc. Dr. Vitiello has received salary support from NIH, income from private practice, and consultant fees from the American Physician Institute for Advanced Professional Studies. Dr. Riddle has received research funding fromNIH and honoraria from the REACH Institute and has served as a member of a Data and Safety Monitoring Board (DSMB) for studies supported by the Best Pharmaceuticals for Children Act and sponsored by the National Institute of Child Health and Human Development (NICHD). He has served on a committee of the Institute ofMedicine, has provided expert witness testimony for Teva Canada, and has received aripiprazole from Bristol-Myers Squibb for an NIMH-sponsored study. Drs. Yenokyan and Ms. Sanyal report no biomedical financial interests or potential conflicts of interest.",
year = "2015",
doi = "10.1016/j.jaac.2015.09.015",
language = "English (US)",
volume = "54",
pages = "1008--1019",
journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
issn = "0890-8567",
publisher = "Elsevier Inc.",
number = "12",
}