OPEN IN READ APP
COMPARATIVE STUDY
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

Olanzapine-divalproex combination versus divalproex monotherapy in the treatment of bipolar mixed episodes: a double-blind, placebo-controlled study

John P Houston, Mauricio Tohen, Elisabeth K Degenhardt, Hassan H Jamal, Lin L L Liu, Terence A Ketter
Journal of Clinical Psychiatry 2009, 70 (11): 1540-7
19778495

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 >or=14 days at levels of 75 to 125 microg/mL with inadequate efficacy (21-item Hamilton Depression Rating Scale [HDRS-21] and Young Mania Rating Scale [YMRS] scores >or=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 (>or=25% HDRS-21 and YMRS decreases, median 7 versus 14 days) and time to response (>or=50% HDRS-21 and YMRS decreases, median 25 versus 49 days) were significantly shorter with adjunctive olanzapine. Increases in weight (total and >or=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.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
19778495
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"