Olanzapine-Divalproex Combination Versus Divalproex Monotherapy in the Treatment of Bipolar Mixed Episodes: A Double-Blind, Placebo-Controlled Study
J Clin Psychiatry 2009;70(11):1540-1547
© Copyright 2015 Physicians Postgraduate Press, Inc.
Purchase This PDF for $40.00
If you are not a paid subscriber, you may purchase the PDF.
(You'll need the free Adobe Acrobat Reader.)
Receive immediate full-text access to JCP. You can subscribe to JCP online-only ($86) or print + online ($156 individual).
With your subscription, receive a free PDF collection of the NCDEU Festschrift articles. Hurry! This offer ends December 31, 2011.
If you are a paid subscriber to JCP and do not yet have a username and password, activate your subscription now.
As a paid subscriber who has activated your subscription, you have access to the HTML and PDF versions of this item.
Click here to login.
Did you forget your password?
Still can't log in? Contact the Circulation Department at 1-800-489-1001 x4 or send email
Objective: This 6-week, randomized, double-blind, placebo-controlled trial used simultaneous depression and mania criteria to compare a single mood stabilizer, divalproex, with and without adjunctive olanzapine in patients with bipolar I disorder experiencing acute mixed episodes.
Method: Two hundred two adults, aged 18 to 60 years, who met DSM-IV-TR criteria for bipolar disorder with a current mixed episode and had been taking divalproex for ≥ 14 days at levels of 75 to 125 µg/mL with inadequate efficacy (21-item Hamilton Depression Rating Scale [HDRS-21] and Young Mania Rating Scale [YMRS] scores ≥ 16) were randomly assigned to olanzapine 5 to 20 mg/d versus placebo augmentation. HDRS-21, YMRS, Clinical Global Impressions for Bipolar Disorder (CGI-BP), hospitalizations, concomitant medications, and adverse events were assessed. Comparisons included changes in both HDRS-21 and YMRS (primary outcome measure), time to partial response and time to response, CGI-BP improvement, hospitalizations, and safety (secondary outcome measures). The study was conducted from December 2006 to February 2008.
Results: Mean (SD) baseline HDRS-21 and YMRS scores were 22.2 (4.5) and 20.9 (4.4), respectively, with 59% female and 51% white subjects. Mean ± SE score changes from baseline across the 6-week treatment period for adjunctive olanzapine (n = 100) versus adjunctive placebo (n = 101) arms, respectively, were −9.37 ± 0.55 versus −7.69 ± 0.54, P = .022, on the HDRS-21 and −10.15 ± 0.44 versus −7.68 ± 0.44 P < .001, on the YMRS. Mean ± SE score changes from baseline to last observation carried forward for CGI-BP measures were −1.34 ± 0.11 for adjunctive olanzapine versus −1.06 ± 0.11 for adjunctive placebo, P = .056. Time to partial response (≥ 25% HDRS-21 and YMRS decreases, median 7 versus 14 days) and time to response (≥ 50% HDRS-21 and YMRS decreases, median 25 versus 49 days) were significantly shorter with adjunctive olanzapine. Increases in weight (total and ≥ 7%) and fasting blood glucose were significantly greater with adjunctive olanzapine.
Conclusion: Adjunctive olanzapine yielded greater and earlier reduction of manic and depressive symptoms in mixed-episode patients with inadequate response to at least 2 weeks of divalproex.
Trial Registration: clinicaltrials.gov Identifier: NCT00402324
See also Commentary on page 1548.
Submitted: November 24, 2008; accepted March 6, 2009.
Online ahead of print: September 22, 2009.
Corresponding author: John P. Houston, MD, PhD, Lilly USA, LLC, Drop Code 4133, Indianapolis, IN 46285 (email@example.com).