A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents

Barbara Geller, Joan L. Luby, Paramjit Joshi, Karen Dineen Wagner, Graham Emslie, John T. Walkup, David A. Axelson, Kristine Bolhofner, Adelaide Robb, Dwight V. Wolf, Mark A Riddle, Boris Birmaher, Nasima Nusrat, Neal D. Ryan, Benedetto Vitiello, Rebecca Tillman, Philip Lavori

Research output: Contribution to journalArticle

Abstract

Context: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Objective: To investigate which medication to administer first to antimanic medication-naive subjects. Design, Setting, and Participants: The Treatment of Early Age Mania (TEAM) study recruited 6-to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patientchoice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments. Interventions: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg). Main Outcome Measures: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents. Results: There were 279 antimanic medication-naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics:100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) μg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; X 1 2 1=16.9, P1 2 1=28.3, P1 2 1=6.4, P=.011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F 1,212=45. 5, P1,212=39.1, P1,213=191.4, P1,212=34.7, P1,212=45.3, P1,213=209.4, P62=11.3, P

Original languageEnglish (US)
Pages (from-to)515-528
Number of pages14
JournalArchives of General Psychiatry
Volume69
Issue number5
DOIs
StatePublished - May 2012

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Risperidone
Valproic Acid
Bipolar Disorder
Lithium
Randomized Controlled Trials
Antimanic Agents
Therapeutics
Outcome Assessment (Health Care)
Lithium Carbonate
Diagnostic and Statistical Manual of Mental Disorders
Prolactin
Psychotic Disorders
Weight Gain
Mania
Medication
Randomized Controlled Trial
Appointments and Schedules
Body Mass Index
Pharmacology
Dose

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Arts and Humanities (miscellaneous)

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A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. / Geller, Barbara; Luby, Joan L.; Joshi, Paramjit; Wagner, Karen Dineen; Emslie, Graham; Walkup, John T.; Axelson, David A.; Bolhofner, Kristine; Robb, Adelaide; Wolf, Dwight V.; Riddle, Mark A; Birmaher, Boris; Nusrat, Nasima; Ryan, Neal D.; Vitiello, Benedetto; Tillman, Rebecca; Lavori, Philip.

In: Archives of General Psychiatry, Vol. 69, No. 5, 05.2012, p. 515-528.

Research output: Contribution to journalArticle

Geller, B, Luby, JL, Joshi, P, Wagner, KD, Emslie, G, Walkup, JT, Axelson, DA, Bolhofner, K, Robb, A, Wolf, DV, Riddle, MA, Birmaher, B, Nusrat, N, Ryan, ND, Vitiello, B, Tillman, R & Lavori, P 2012, 'A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents', Archives of General Psychiatry, vol. 69, no. 5, pp. 515-528. https://doi.org/10.1001/archgenpsychiatry.2011.1508
Geller, Barbara ; Luby, Joan L. ; Joshi, Paramjit ; Wagner, Karen Dineen ; Emslie, Graham ; Walkup, John T. ; Axelson, David A. ; Bolhofner, Kristine ; Robb, Adelaide ; Wolf, Dwight V. ; Riddle, Mark A ; Birmaher, Boris ; Nusrat, Nasima ; Ryan, Neal D. ; Vitiello, Benedetto ; Tillman, Rebecca ; Lavori, Philip. / A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. In: Archives of General Psychiatry. 2012 ; Vol. 69, No. 5. pp. 515-528.
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abstract = "Context: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Objective: To investigate which medication to administer first to antimanic medication-naive subjects. Design, Setting, and Participants: The Treatment of Early Age Mania (TEAM) study recruited 6-to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patientchoice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments. Interventions: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg). Main Outcome Measures: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents. Results: There were 279 antimanic medication-naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2{\%} female) who had the following characteristics:100{\%} elated mood and/or grandiosity, 77.1{\%} psychosis, 97.5{\%} mixed mania, 99.3{\%} daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) μg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5{\%} vs 35.6{\%}; X 1 2 1=16.9, P1 2 1=28.3, P1 2 1=6.4, P=.011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F 1,212=45. 5, P1,212=39.1, P1,213=191.4, P1,212=34.7, P1,212=45.3, P1,213=209.4, P62=11.3, P",
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T1 - A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents

AU - Geller, Barbara

AU - Luby, Joan L.

AU - Joshi, Paramjit

AU - Wagner, Karen Dineen

AU - Emslie, Graham

AU - Walkup, John T.

AU - Axelson, David A.

AU - Bolhofner, Kristine

AU - Robb, Adelaide

AU - Wolf, Dwight V.

AU - Riddle, Mark A

AU - Birmaher, Boris

AU - Nusrat, Nasima

AU - Ryan, Neal D.

AU - Vitiello, Benedetto

AU - Tillman, Rebecca

AU - Lavori, Philip

PY - 2012/5

Y1 - 2012/5

N2 - Context: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Objective: To investigate which medication to administer first to antimanic medication-naive subjects. Design, Setting, and Participants: The Treatment of Early Age Mania (TEAM) study recruited 6-to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patientchoice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments. Interventions: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg). Main Outcome Measures: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents. Results: There were 279 antimanic medication-naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics:100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) μg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; X 1 2 1=16.9, P1 2 1=28.3, P1 2 1=6.4, P=.011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F 1,212=45. 5, P1,212=39.1, P1,213=191.4, P1,212=34.7, P1,212=45.3, P1,213=209.4, P62=11.3, P

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