A Randomized, Placebo-Controlled, Multicenter Study of Divalproex Sodium Extended Release in the Treatment of Acute Mania
J Clin Psychiatry 2006;67:1501-1510
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Objective: The efficacy and safety of
divalproex sodium extended release (divalproex ER) were evaluated in patients hospitalized for
acute mania associated with bipolar I disorder, manic
or mixed type (DSM-IV-TR criteria).
Method: Following screening and washout
of psychotropic medications, 377 patients were randomly assigned in a 1:1 ratio to 21 days
of double-blind treatment with divalproex ER (N = 192) or placebo (N = 185). Daily dosage was
initiated at 25 mg/kg, increased 500 mg on day 3, and adjusted to serum valproate concentrations
of 85 to 125 mg/mL. The Mania Rating Scale (MRS) was used to assess efficacy. Patients
remained hospitalized at least 15 days during blinded
treatment. The study was conducted from April 2003 to May 2004.
Results: Improvement from baseline on
the MRS was significantly greater among patients who received divalproex ER compared with
placebo at the first on-treatment rating
assessment, day 5, and all subsequent ratings through day
21 (p = .013). Furthermore, the proportion of patients achieving at least 50% improvement
from baseline in MRS was significantly higher in
patients receiving divalproex ER (48%) than in patients receiving placebo (34%) (p = .012). Five
of the 11 MRS items improved significantly more in patients receiving divalproex ER than
placebo: less need for sleep (p <= .01), more energetic
(p <= .05), increased activity (p <= .05),
generalized motor hyperactivity (p <= .05), and
racing thoughts (p <= .001). Side effects associated
with divalproex ER included somnolence, dizziness, and gastrointestinal complaints.
Conclusion: The results indicate that
divalproex ER is effective and safe for the treatment
of mania episodes in bipolar I patients.
Registration: ClinicalTrials.gov identifier NCT00060905.