Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania

A randomized, 12-week, double-blind study

Mauricio Tohen, Eduard Vieta, Guy M. Goodwin, Bin Sun, Jay D. Amsterdam, Michael Banov, Anantha Shekhar, Scott T. Aaronson, Leonid Bardenstein, Iosif Grecu-Gaboş, Vladimir Tochilov, Dan Prelipceanu, Heather S. Oliff, Ludmila Kryzhanovskaya, Charles Bowden

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Objective: To evaluate the efficacy and safety of olanzapine, divalproex, and placebo in a randomized, double-blind trial in mild to moderate mania (DSM-IV-TR criteria). Method: The study was conducted from October 2004 to December 2006. A total of 521 patients from private practices, hospitals, and university clinics were randomly assigned to olanzapine (5-20 mg/day), divalproex (500-2500 mg/day), or placebo for 3 weeks; those completing continued with a 9-week double-blind extension. Efficacy (mean change in Young Mania Rating Scale [YMRS] total score was the primary outcome) and safety were assessed. Results: After 3 weeks of treatment, olanzapine-treated (N = 215) and placebo-treated (N = 105) patients significantly differed in YMRS baseline-to-endpoint total score change (p = .034; least squares [LS] mean: -9.4 and -7.4, respectively). Such changes were not significantly different between olanzapine vs. divalproex (N = 201) or divalproex vs. placebo. After 12 weeks of treatment, olanzapine-and divalproex-treated patients significantly differed in YMRS baseline-to-endpoint changes (p = .004; LS mean: -13.3 and -10.7, respectively). Of observed cases, 35.4% (35/99; 3 weeks) to 57.1% (28/49; 12 weeks) had valproate plasma concentrations lower than the recommended valproate therapeutic range, but these patients' YMRS scores were lower than those of patients with valproate concentrations above/within range. Compared with divalproex, after 12 weeks, olanzapine-treated patients had significant increases in weight (p < .001) and in glucose (p < .001), triglyceride (p = .003), cholesterol (p = .024), uric acid (p = .027), and prolactin (p < .001) levels. Divalproex-treated patients had significant decreases in leukocytes (p = .044) and platelets (p < .001) compared with olanzapine after 12 weeks of treatment. The incidence of potentially clinically significant weight gain (≥ 7% from baseline) was higher with olanzapine than with divalproex (3-week: p = .064, 6.4% vs. 2.7%; 12-week: p = .002, 18.8% vs. 8.5%; respectively). Conclusion: Olanzapine was significantly more efficacious than placebo but not divalproex at 3 weeks and significantly more efficacious than divalproex at 12 weeks. Olanzapine-treated patients had significantly greater increases in weight and in glucose, cholesterol, triglyceride, uric acid, and prolactin levels than divalproex-treated patients. Trial Registration: clinicaltrials.gov Identifier: NCT00094549.

Original languageEnglish
Pages (from-to)1776-1789
Number of pages14
JournalJournal of Clinical Psychiatry
Volume69
Issue number11
StatePublished - Nov 2008

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olanzapine
Valproic Acid
Bipolar Disorder
Double-Blind Method
Placebos
Therapeutics
Uric Acid
Least-Squares Analysis
Prolactin
Triglycerides
Cholesterol

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Tohen, M., Vieta, E., Goodwin, G. M., Sun, B., Amsterdam, J. D., Banov, M., ... Bowden, C. (2008). Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania: A randomized, 12-week, double-blind study. Journal of Clinical Psychiatry, 69(11), 1776-1789.

Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania : A randomized, 12-week, double-blind study. / Tohen, Mauricio; Vieta, Eduard; Goodwin, Guy M.; Sun, Bin; Amsterdam, Jay D.; Banov, Michael; Shekhar, Anantha; Aaronson, Scott T.; Bardenstein, Leonid; Grecu-Gaboş, Iosif; Tochilov, Vladimir; Prelipceanu, Dan; Oliff, Heather S.; Kryzhanovskaya, Ludmila; Bowden, Charles.

In: Journal of Clinical Psychiatry, Vol. 69, No. 11, 11.2008, p. 1776-1789.

Research output: Contribution to journalArticle

Tohen, M, Vieta, E, Goodwin, GM, Sun, B, Amsterdam, JD, Banov, M, Shekhar, A, Aaronson, ST, Bardenstein, L, Grecu-Gaboş, I, Tochilov, V, Prelipceanu, D, Oliff, HS, Kryzhanovskaya, L & Bowden, C 2008, 'Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania: A randomized, 12-week, double-blind study', Journal of Clinical Psychiatry, vol. 69, no. 11, pp. 1776-1789.
Tohen, Mauricio ; Vieta, Eduard ; Goodwin, Guy M. ; Sun, Bin ; Amsterdam, Jay D. ; Banov, Michael ; Shekhar, Anantha ; Aaronson, Scott T. ; Bardenstein, Leonid ; Grecu-Gaboş, Iosif ; Tochilov, Vladimir ; Prelipceanu, Dan ; Oliff, Heather S. ; Kryzhanovskaya, Ludmila ; Bowden, Charles. / Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania : A randomized, 12-week, double-blind study. In: Journal of Clinical Psychiatry. 2008 ; Vol. 69, No. 11. pp. 1776-1789.
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abstract = "Objective: To evaluate the efficacy and safety of olanzapine, divalproex, and placebo in a randomized, double-blind trial in mild to moderate mania (DSM-IV-TR criteria). Method: The study was conducted from October 2004 to December 2006. A total of 521 patients from private practices, hospitals, and university clinics were randomly assigned to olanzapine (5-20 mg/day), divalproex (500-2500 mg/day), or placebo for 3 weeks; those completing continued with a 9-week double-blind extension. Efficacy (mean change in Young Mania Rating Scale [YMRS] total score was the primary outcome) and safety were assessed. Results: After 3 weeks of treatment, olanzapine-treated (N = 215) and placebo-treated (N = 105) patients significantly differed in YMRS baseline-to-endpoint total score change (p = .034; least squares [LS] mean: -9.4 and -7.4, respectively). Such changes were not significantly different between olanzapine vs. divalproex (N = 201) or divalproex vs. placebo. After 12 weeks of treatment, olanzapine-and divalproex-treated patients significantly differed in YMRS baseline-to-endpoint changes (p = .004; LS mean: -13.3 and -10.7, respectively). Of observed cases, 35.4{\%} (35/99; 3 weeks) to 57.1{\%} (28/49; 12 weeks) had valproate plasma concentrations lower than the recommended valproate therapeutic range, but these patients' YMRS scores were lower than those of patients with valproate concentrations above/within range. Compared with divalproex, after 12 weeks, olanzapine-treated patients had significant increases in weight (p < .001) and in glucose (p < .001), triglyceride (p = .003), cholesterol (p = .024), uric acid (p = .027), and prolactin (p < .001) levels. Divalproex-treated patients had significant decreases in leukocytes (p = .044) and platelets (p < .001) compared with olanzapine after 12 weeks of treatment. The incidence of potentially clinically significant weight gain (≥ 7{\%} from baseline) was higher with olanzapine than with divalproex (3-week: p = .064, 6.4{\%} vs. 2.7{\%}; 12-week: p = .002, 18.8{\%} vs. 8.5{\%}; respectively). Conclusion: Olanzapine was significantly more efficacious than placebo but not divalproex at 3 weeks and significantly more efficacious than divalproex at 12 weeks. Olanzapine-treated patients had significantly greater increases in weight and in glucose, cholesterol, triglyceride, uric acid, and prolactin levels than divalproex-treated patients. Trial Registration: clinicaltrials.gov Identifier: NCT00094549.",
author = "Mauricio Tohen and Eduard Vieta and Goodwin, {Guy M.} and Bin Sun and Amsterdam, {Jay D.} and Michael Banov and Anantha Shekhar and Aaronson, {Scott T.} and Leonid Bardenstein and Iosif Grecu-Gaboş and Vladimir Tochilov and Dan Prelipceanu and Oliff, {Heather S.} and Ludmila Kryzhanovskaya and Charles Bowden",
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TY - JOUR

T1 - Olanzapine versus divalproex versus placebo in the treatment of mild to moderate mania

T2 - A randomized, 12-week, double-blind study

AU - Tohen, Mauricio

AU - Vieta, Eduard

AU - Goodwin, Guy M.

AU - Sun, Bin

AU - Amsterdam, Jay D.

AU - Banov, Michael

AU - Shekhar, Anantha

AU - Aaronson, Scott T.

AU - Bardenstein, Leonid

AU - Grecu-Gaboş, Iosif

AU - Tochilov, Vladimir

AU - Prelipceanu, Dan

AU - Oliff, Heather S.

AU - Kryzhanovskaya, Ludmila

AU - Bowden, Charles

PY - 2008/11

Y1 - 2008/11

N2 - Objective: To evaluate the efficacy and safety of olanzapine, divalproex, and placebo in a randomized, double-blind trial in mild to moderate mania (DSM-IV-TR criteria). Method: The study was conducted from October 2004 to December 2006. A total of 521 patients from private practices, hospitals, and university clinics were randomly assigned to olanzapine (5-20 mg/day), divalproex (500-2500 mg/day), or placebo for 3 weeks; those completing continued with a 9-week double-blind extension. Efficacy (mean change in Young Mania Rating Scale [YMRS] total score was the primary outcome) and safety were assessed. Results: After 3 weeks of treatment, olanzapine-treated (N = 215) and placebo-treated (N = 105) patients significantly differed in YMRS baseline-to-endpoint total score change (p = .034; least squares [LS] mean: -9.4 and -7.4, respectively). Such changes were not significantly different between olanzapine vs. divalproex (N = 201) or divalproex vs. placebo. After 12 weeks of treatment, olanzapine-and divalproex-treated patients significantly differed in YMRS baseline-to-endpoint changes (p = .004; LS mean: -13.3 and -10.7, respectively). Of observed cases, 35.4% (35/99; 3 weeks) to 57.1% (28/49; 12 weeks) had valproate plasma concentrations lower than the recommended valproate therapeutic range, but these patients' YMRS scores were lower than those of patients with valproate concentrations above/within range. Compared with divalproex, after 12 weeks, olanzapine-treated patients had significant increases in weight (p < .001) and in glucose (p < .001), triglyceride (p = .003), cholesterol (p = .024), uric acid (p = .027), and prolactin (p < .001) levels. Divalproex-treated patients had significant decreases in leukocytes (p = .044) and platelets (p < .001) compared with olanzapine after 12 weeks of treatment. The incidence of potentially clinically significant weight gain (≥ 7% from baseline) was higher with olanzapine than with divalproex (3-week: p = .064, 6.4% vs. 2.7%; 12-week: p = .002, 18.8% vs. 8.5%; respectively). Conclusion: Olanzapine was significantly more efficacious than placebo but not divalproex at 3 weeks and significantly more efficacious than divalproex at 12 weeks. Olanzapine-treated patients had significantly greater increases in weight and in glucose, cholesterol, triglyceride, uric acid, and prolactin levels than divalproex-treated patients. Trial Registration: clinicaltrials.gov Identifier: NCT00094549.

AB - Objective: To evaluate the efficacy and safety of olanzapine, divalproex, and placebo in a randomized, double-blind trial in mild to moderate mania (DSM-IV-TR criteria). Method: The study was conducted from October 2004 to December 2006. A total of 521 patients from private practices, hospitals, and university clinics were randomly assigned to olanzapine (5-20 mg/day), divalproex (500-2500 mg/day), or placebo for 3 weeks; those completing continued with a 9-week double-blind extension. Efficacy (mean change in Young Mania Rating Scale [YMRS] total score was the primary outcome) and safety were assessed. Results: After 3 weeks of treatment, olanzapine-treated (N = 215) and placebo-treated (N = 105) patients significantly differed in YMRS baseline-to-endpoint total score change (p = .034; least squares [LS] mean: -9.4 and -7.4, respectively). Such changes were not significantly different between olanzapine vs. divalproex (N = 201) or divalproex vs. placebo. After 12 weeks of treatment, olanzapine-and divalproex-treated patients significantly differed in YMRS baseline-to-endpoint changes (p = .004; LS mean: -13.3 and -10.7, respectively). Of observed cases, 35.4% (35/99; 3 weeks) to 57.1% (28/49; 12 weeks) had valproate plasma concentrations lower than the recommended valproate therapeutic range, but these patients' YMRS scores were lower than those of patients with valproate concentrations above/within range. Compared with divalproex, after 12 weeks, olanzapine-treated patients had significant increases in weight (p < .001) and in glucose (p < .001), triglyceride (p = .003), cholesterol (p = .024), uric acid (p = .027), and prolactin (p < .001) levels. Divalproex-treated patients had significant decreases in leukocytes (p = .044) and platelets (p < .001) compared with olanzapine after 12 weeks of treatment. The incidence of potentially clinically significant weight gain (≥ 7% from baseline) was higher with olanzapine than with divalproex (3-week: p = .064, 6.4% vs. 2.7%; 12-week: p = .002, 18.8% vs. 8.5%; respectively). Conclusion: Olanzapine was significantly more efficacious than placebo but not divalproex at 3 weeks and significantly more efficacious than divalproex at 12 weeks. Olanzapine-treated patients had significantly greater increases in weight and in glucose, cholesterol, triglyceride, uric acid, and prolactin levels than divalproex-treated patients. Trial Registration: clinicaltrials.gov Identifier: NCT00094549.

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