TY - JOUR
T1 - Divalproex in the treatment of acute bipolar depression
T2 - A preliminary double-blind, randomized, placebo-controlled pilot study
AU - Ghaemi, S. Nassir
AU - Gilmer, William S.
AU - Goldberg, Joseph F.
AU - Zablotsky, Benjamin
AU - Kemp, David E.
AU - Kelley, Mary E.
AU - Bauer, Amber D.
AU - Fleck, Jenelle
AU - Filkowski, Megan M.
AU - Stan, Vanessa A.
AU - Dunn, Robert T.
PY - 2007/12
Y1 - 2007/12
N2 - Objective: To determine the efficacy of divalproex (extended release) in the treatment of acute nonrefractory bipolar depression. Method: In a stratified, double-blind, randomized, placebo-controlled trial, 18 acutely depressed bipolar outpatients (DSM-IV criteria) received either divalproex monotherapy (target dose level, 70-90 ng/dL) (N = 9) or placebo (N = 9) for 6 weeks. Patients were recruited between January 2004 and May 2005. Clinical assessment on the Montgomery-Asberg Depression Rating Scale (MADRS) determined primary efficacy. Results: The divalproex treatment group showed significantly greater reduction in MADRS scores compared to placebo (group x time interaction, p = .0078). Absolute effect size of estimated MADRS total score reduction over time was 13.6 points with divalproex versus 1.4 points with placebo (p = .003, linear growth curve model). Standardized effect size was large (Cohen d = 0.81). MADRS item analyses demonstrated improvement in core mood symptoms more than in anxiety or insomnia symptoms. There was also a modest but significant association between MADRS and Mania Rating Scale scores in the divalproex group (r = 0.29, df = 51, p = .03), but not in the placebo group (r = -0.15, df = 35, p = .36). Conclusions: Divalproex appeared to be an effective treatment for acute nonrefractory bipolar depression, which is consistent with previous small randomized studies. Some evidence of benefit in the depressive mixed state was observed. Confirmation or refutation with larger randomized clinical trials is warranted. Clinical trial registration: ClinicalTrials.gov identifier NCT00226343.
AB - Objective: To determine the efficacy of divalproex (extended release) in the treatment of acute nonrefractory bipolar depression. Method: In a stratified, double-blind, randomized, placebo-controlled trial, 18 acutely depressed bipolar outpatients (DSM-IV criteria) received either divalproex monotherapy (target dose level, 70-90 ng/dL) (N = 9) or placebo (N = 9) for 6 weeks. Patients were recruited between January 2004 and May 2005. Clinical assessment on the Montgomery-Asberg Depression Rating Scale (MADRS) determined primary efficacy. Results: The divalproex treatment group showed significantly greater reduction in MADRS scores compared to placebo (group x time interaction, p = .0078). Absolute effect size of estimated MADRS total score reduction over time was 13.6 points with divalproex versus 1.4 points with placebo (p = .003, linear growth curve model). Standardized effect size was large (Cohen d = 0.81). MADRS item analyses demonstrated improvement in core mood symptoms more than in anxiety or insomnia symptoms. There was also a modest but significant association between MADRS and Mania Rating Scale scores in the divalproex group (r = 0.29, df = 51, p = .03), but not in the placebo group (r = -0.15, df = 35, p = .36). Conclusions: Divalproex appeared to be an effective treatment for acute nonrefractory bipolar depression, which is consistent with previous small randomized studies. Some evidence of benefit in the depressive mixed state was observed. Confirmation or refutation with larger randomized clinical trials is warranted. Clinical trial registration: ClinicalTrials.gov identifier NCT00226343.
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U2 - 10.4088/JCP.v68n1203
DO - 10.4088/JCP.v68n1203
M3 - Article
C2 - 18162014
AN - SCOPUS:38049061055
SN - 0160-6689
VL - 68
SP - 1840
EP - 1844
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
IS - 12
ER -