TY - JOUR
T1 - Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study
AU - Salpekar, Jay A.
AU - Joshi, Paramjit T.
AU - Axelson, David A.
AU - Reinblatt, Shauna P.
AU - Yenokyan, Gayane
AU - Sanyal, Abanti
AU - Walkup, John T.
AU - Vitiello, Benedetto
AU - Luby, Joan L.
AU - Wagner, Karen Dineen
AU - Nusrat, Nasima
AU - Riddle, Mark A.
N1 - 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 from its 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. Salpekar has served as a member of a Data and Safety Monitoring Board (DSMB) for studies sponsored by the NIMH Intramural Program. He has received honoraria from the Gulf Child Mental and Behavioral Health Society and has served as a consultant for Sunovion. Dr. Joshi holds leadership positions as president of AACAP for the term 2013 to 2015 and as a psychiatry director of the ABPN. Dr. Axelson has served as a consultant for Janssen Research and Development and has received royalties from Wolters Kluwer. Dr. Reinblatt has received research funding from NIMH and honoraria from the Osler Institute and the National Board of Medical Examiners. 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 SyndromeeCenter for Disease Control and Prevention outreach educational programs, 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. Vitiello has received salary support from NIH, income from private practice, and consultant fees from the American Physician Institute for Advanced Professional Studies. Dr. Luby has received grant or research support from NIMH. She has received royalties from Guilford Press. 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. Riddle has received research funding from NIH and honoraria from the REACH Institute and has served as a member of a DSMB for studies supported by the Best Pharmaceuticals for Children Act and sponsored by the National Institute of Child Health and Human Development. He has served on a committee of the Institute of Medicine, has provided expert witness testimony for Teva Canada, and has received aripiprazole from Bristol-Myers Squibb for an NIMH-sponsored study. Drs. Yenokyan and Nusrat and Ms. Sanyal report no biomedical financial interests or potential conflicts of interest.
Publisher Copyright:
© 2015 American Academy of Child and Adolescent Psychiatry.
PY - 2015
Y1 - 2015
N2 - Objective To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder. Method The Treatment of Early Age Mania (TEAM) study is a multicenter, prospective, randomized, masked comparison of divalproex sodium (VAL), lithium carbonate (LI), and risperidone (RISP) in an 8-week parallel clinical trial. A total of 279 children and adolescents with DSM-IV diagnoses of bipolar I disorder, mixed or manic, aged 6 to 15 years were enrolled. The primary outcome measure was improvement on the Clinical Global Impression scale for depression (CGI-BP-I-D). Secondary outcome measures included the Children's Depression Rating Scale (CDRS-R) and suicidality status. Statistics included longitudinal analysis of outcomes using generalized linear mixed models with random intercept both for the complete data set and by using last observation carried forward. Results CGI-BP-I-D ratings were better in the RISP group (60.7%) as compared to the LI (42.2%; p =.03) or VAL (35.0%; p =.003) groups from baseline to the end of the study. CDRS scores in all treatment groups improved equally by study end. In week 1, scores were lower with RISP compared to VAL (mean = 4.72, 95% CI = 2.67, 6.78), and compared to LI (mean = 3.63, 95% CI = 1.51, 5.74), although group differences were not present by the end of the study. Suicidality was infrequent, and there was no overall effect of treatment on suicidality ratings. Conclusion Depressive symptoms, present in the acutely manic or mixed phase of pediatric bipolar disorder, improved with all 3 medications, though RISP appeared to yield more rapid improvement than LI or VAL and was superior using a global categorical outcome.
AB - Objective To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder. Method The Treatment of Early Age Mania (TEAM) study is a multicenter, prospective, randomized, masked comparison of divalproex sodium (VAL), lithium carbonate (LI), and risperidone (RISP) in an 8-week parallel clinical trial. A total of 279 children and adolescents with DSM-IV diagnoses of bipolar I disorder, mixed or manic, aged 6 to 15 years were enrolled. The primary outcome measure was improvement on the Clinical Global Impression scale for depression (CGI-BP-I-D). Secondary outcome measures included the Children's Depression Rating Scale (CDRS-R) and suicidality status. Statistics included longitudinal analysis of outcomes using generalized linear mixed models with random intercept both for the complete data set and by using last observation carried forward. Results CGI-BP-I-D ratings were better in the RISP group (60.7%) as compared to the LI (42.2%; p =.03) or VAL (35.0%; p =.003) groups from baseline to the end of the study. CDRS scores in all treatment groups improved equally by study end. In week 1, scores were lower with RISP compared to VAL (mean = 4.72, 95% CI = 2.67, 6.78), and compared to LI (mean = 3.63, 95% CI = 1.51, 5.74), although group differences were not present by the end of the study. Suicidality was infrequent, and there was no overall effect of treatment on suicidality ratings. Conclusion Depressive symptoms, present in the acutely manic or mixed phase of pediatric bipolar disorder, improved with all 3 medications, though RISP appeared to yield more rapid improvement than LI or VAL and was superior using a global categorical outcome.
KW - bipolar
KW - clinical trial
KW - depression
KW - pediatrics
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=84951304924&partnerID=8YFLogxK
U2 - 10.1016/j.jaac.2015.09.016
DO - 10.1016/j.jaac.2015.09.016
M3 - Article
C2 - 26598475
AN - SCOPUS:84951304924
SN - 0890-8567
VL - 54
SP - 999-1007.e4
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
IS - 12
ER -