A randomized, placebo-controlled, multicenter study of divalproex sodium extended-release in the acute treatment of mania

Robert M A Hirschfeld, Charles L. Bowden, Namita V. Vigna, Patricia Wozniak, Michelle Collins

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: Divalproex sodium extended-release (ER) was examined for the treatment of acute mania in adults in 2 randomized, placebo-controlled clinical trials. One study demonstrated statistically significant improvements in mania symptoms compared to placebo, while an earlier study did not. Results of the earlier study are presented here. Method: A total of 225 DSM-IV-diagnosed bipolar I disorder patients were randomly assigned in a 2:1 ratio to 21 days of double-blind treatment with divalproex ER (n = 147) or placebo (n = 78). The daily divalproex ER dosage was initiated at 20 mg/kg. The primary efficacy variable was the change from baseline to final evaluation in Mania Rating Scale (MRS) score. Subjects were discontinued from the study if they were discharged from the hospital or if they met prespecified improvement criteria. The study was conducted from May 1998 to July 1999 at centers in the United States. Results: There was no statistically significant difference in MRS score change from baseline to final for patients treated with divalproex ER compared with those treated with placebo. With the exception of back pain and constipation, adverse event rates between placebo and divalproex ER were very similar. A large proportion of patients prematurely discontinued study treatment (divalproex ER: 83%, placebo: 82%). The mean daily dose of divalproex ER was 2,211 mg with a mean maximum serum valproic acid concentration of 77.9 μg/mL. Conclusions: The results of the current study did not demonstrate statistically significant improvement in mania symptoms associated with divalproex ER treatment compared to placebo. A number of methodological considerations may have contributed to the negative findings, including allowance for early study discontinuation and lower than optimal dosing. Trial Registration: clinicaltrials.gov Identifier: NCT00060905

Original languageEnglish (US)
Pages (from-to)426-432
Number of pages7
JournalJournal of Clinical Psychiatry
Volume71
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Valproic Acid
Bipolar Disorder
Multicenter Studies
Placebos
Therapeutics
Constipation
Back Pain
Diagnostic and Statistical Manual of Mental Disorders
Randomized Controlled Trials
Serum

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

A randomized, placebo-controlled, multicenter study of divalproex sodium extended-release in the acute treatment of mania. / Hirschfeld, Robert M A; Bowden, Charles L.; Vigna, Namita V.; Wozniak, Patricia; Collins, Michelle.

In: Journal of Clinical Psychiatry, Vol. 71, No. 4, 04.2010, p. 426-432.

Research output: Contribution to journalArticle

Hirschfeld, Robert M A ; Bowden, Charles L. ; Vigna, Namita V. ; Wozniak, Patricia ; Collins, Michelle. / A randomized, placebo-controlled, multicenter study of divalproex sodium extended-release in the acute treatment of mania. In: Journal of Clinical Psychiatry. 2010 ; Vol. 71, No. 4. pp. 426-432.
@article{7ec49610f23d4a89940775ed5cb45eab,
title = "A randomized, placebo-controlled, multicenter study of divalproex sodium extended-release in the acute treatment of mania",
abstract = "Objective: Divalproex sodium extended-release (ER) was examined for the treatment of acute mania in adults in 2 randomized, placebo-controlled clinical trials. One study demonstrated statistically significant improvements in mania symptoms compared to placebo, while an earlier study did not. Results of the earlier study are presented here. Method: A total of 225 DSM-IV-diagnosed bipolar I disorder patients were randomly assigned in a 2:1 ratio to 21 days of double-blind treatment with divalproex ER (n = 147) or placebo (n = 78). The daily divalproex ER dosage was initiated at 20 mg/kg. The primary efficacy variable was the change from baseline to final evaluation in Mania Rating Scale (MRS) score. Subjects were discontinued from the study if they were discharged from the hospital or if they met prespecified improvement criteria. The study was conducted from May 1998 to July 1999 at centers in the United States. Results: There was no statistically significant difference in MRS score change from baseline to final for patients treated with divalproex ER compared with those treated with placebo. With the exception of back pain and constipation, adverse event rates between placebo and divalproex ER were very similar. A large proportion of patients prematurely discontinued study treatment (divalproex ER: 83{\%}, placebo: 82{\%}). The mean daily dose of divalproex ER was 2,211 mg with a mean maximum serum valproic acid concentration of 77.9 μg/mL. Conclusions: The results of the current study did not demonstrate statistically significant improvement in mania symptoms associated with divalproex ER treatment compared to placebo. A number of methodological considerations may have contributed to the negative findings, including allowance for early study discontinuation and lower than optimal dosing. Trial Registration: clinicaltrials.gov Identifier: NCT00060905",
author = "Hirschfeld, {Robert M A} and Bowden, {Charles L.} and Vigna, {Namita V.} and Patricia Wozniak and Michelle Collins",
year = "2010",
month = "4",
doi = "10.4088/JCP.08m04960yel",
language = "English (US)",
volume = "71",
pages = "426--432",
journal = "Journal of Clinical Psychiatry",
issn = "0160-6689",
publisher = "Physicians Postgraduate Press Inc.",
number = "4",

}

TY - JOUR

T1 - A randomized, placebo-controlled, multicenter study of divalproex sodium extended-release in the acute treatment of mania

AU - Hirschfeld, Robert M A

AU - Bowden, Charles L.

AU - Vigna, Namita V.

AU - Wozniak, Patricia

AU - Collins, Michelle

PY - 2010/4

Y1 - 2010/4

N2 - Objective: Divalproex sodium extended-release (ER) was examined for the treatment of acute mania in adults in 2 randomized, placebo-controlled clinical trials. One study demonstrated statistically significant improvements in mania symptoms compared to placebo, while an earlier study did not. Results of the earlier study are presented here. Method: A total of 225 DSM-IV-diagnosed bipolar I disorder patients were randomly assigned in a 2:1 ratio to 21 days of double-blind treatment with divalproex ER (n = 147) or placebo (n = 78). The daily divalproex ER dosage was initiated at 20 mg/kg. The primary efficacy variable was the change from baseline to final evaluation in Mania Rating Scale (MRS) score. Subjects were discontinued from the study if they were discharged from the hospital or if they met prespecified improvement criteria. The study was conducted from May 1998 to July 1999 at centers in the United States. Results: There was no statistically significant difference in MRS score change from baseline to final for patients treated with divalproex ER compared with those treated with placebo. With the exception of back pain and constipation, adverse event rates between placebo and divalproex ER were very similar. A large proportion of patients prematurely discontinued study treatment (divalproex ER: 83%, placebo: 82%). The mean daily dose of divalproex ER was 2,211 mg with a mean maximum serum valproic acid concentration of 77.9 μg/mL. Conclusions: The results of the current study did not demonstrate statistically significant improvement in mania symptoms associated with divalproex ER treatment compared to placebo. A number of methodological considerations may have contributed to the negative findings, including allowance for early study discontinuation and lower than optimal dosing. Trial Registration: clinicaltrials.gov Identifier: NCT00060905

AB - Objective: Divalproex sodium extended-release (ER) was examined for the treatment of acute mania in adults in 2 randomized, placebo-controlled clinical trials. One study demonstrated statistically significant improvements in mania symptoms compared to placebo, while an earlier study did not. Results of the earlier study are presented here. Method: A total of 225 DSM-IV-diagnosed bipolar I disorder patients were randomly assigned in a 2:1 ratio to 21 days of double-blind treatment with divalproex ER (n = 147) or placebo (n = 78). The daily divalproex ER dosage was initiated at 20 mg/kg. The primary efficacy variable was the change from baseline to final evaluation in Mania Rating Scale (MRS) score. Subjects were discontinued from the study if they were discharged from the hospital or if they met prespecified improvement criteria. The study was conducted from May 1998 to July 1999 at centers in the United States. Results: There was no statistically significant difference in MRS score change from baseline to final for patients treated with divalproex ER compared with those treated with placebo. With the exception of back pain and constipation, adverse event rates between placebo and divalproex ER were very similar. A large proportion of patients prematurely discontinued study treatment (divalproex ER: 83%, placebo: 82%). The mean daily dose of divalproex ER was 2,211 mg with a mean maximum serum valproic acid concentration of 77.9 μg/mL. Conclusions: The results of the current study did not demonstrate statistically significant improvement in mania symptoms associated with divalproex ER treatment compared to placebo. A number of methodological considerations may have contributed to the negative findings, including allowance for early study discontinuation and lower than optimal dosing. Trial Registration: clinicaltrials.gov Identifier: NCT00060905

UR - http://www.scopus.com/inward/record.url?scp=77951070202&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951070202&partnerID=8YFLogxK

U2 - 10.4088/JCP.08m04960yel

DO - 10.4088/JCP.08m04960yel

M3 - Article

VL - 71

SP - 426

EP - 432

JO - Journal of Clinical Psychiatry

JF - Journal of Clinical Psychiatry

SN - 0160-6689

IS - 4

ER -