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.

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).

METHOD: 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.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00278772.