title: Randomized, double-blind, placebo-controlled study of divalproex extended release loading monotherapy in ambulatory bipolar spectrum disorder patients with moderate-to-severe hypomania or mild mania.
abstract: OBJECTIVE
  To determine whether divalproex extended release (ER) would be effective in outpatients with DSM-IV-TR-diagnosed ambulatory bipolar spectrum disorder (BSD) and moderate-to-severe hypomanic or mild manic symptoms (hypomania/mild mania).
  
  
  METHODS
  An 8-week, randomized, double-blind, placebo-controlled trial of divalproex ER oral loading (begun at 15 mg/kg/d and titrated to a maximum of 30 mg/kg/d) in ambulatory BSD with hypomania/mild mania patients, operationally defined as a Young Mania Rating Scale (YMRS) score >or= 10 but < 21 at baseline and at 1 other study visit at least 3 days apart over the 2 weeks before baseline, was conducted. Patients were enrolled from October 2003 through November 2007.
  
  
  RESULTS
  Sixty patients (n = 30 in the divalproex ER group) had at least 1 postbaseline assessment. The divalproex ER group showed a significantly greater rate of reduction in mean total YMRS score than the placebo group (longitudinal analysis, P = .024). The divalproex ER group also showed more improvement in depressive symptoms the greater the severity of baseline depression (P = .11 for analysis of covariance treatment-by-baseline interaction). Baseline-to-endpoint change scores using last-observation-carried-forward showed that divalproex ER was associated with a marginally significant change in mean total YMRS score (P = .080). Comparable numbers of patients discontinued divalproex ER (n = 17) and placebo (n = 15), including those that discontinued use because of adverse events (n = 4 and 3, respectively).
  
  
  CONCLUSIONS
  Divalproex ER begun at 15 mg/kg/d was superior to placebo in reducing hypomanic/mild manic symptoms in ambulatory BSD. It was associated with fairly good tolerability but a high discontinuation rate. Controlled trials of divalproex ER and other mood stabilizers in larger groups of ambulatory BSD patients with hypomanic/mild manic symptoms appear warranted.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00278772.
authors.affiliation: 4075 Old Western Row Road, Mason, OH 45040, USA. susan.mcelroy@lindnercenter.org
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.forename: Brian E
authors.initials: BE
authors.lastname: Martens
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Creech
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Welge
authors.forename: Lena
authors.initials: L
authors.lastname: Jefferson
authors.forename: Anna I
authors.initials: AI
authors.lastname: Guerdjikova
authors.forename: Paul E
authors.initials: PE
authors.lastname: Keck
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D003692:Delayed-Action Preparations; D014635:Valproic Acid