A double-blind, placebo-controlled pilot study of galantamine to improve cognitive dysfunction in minimally symptomatic bipolar disorder.

OBJECTIVE: There is increasing evidence that cognitive impairment is common in patients with bipolar disorder. The purpose of this study was to determine whether galantamine augmentation improved cognition in patients with euthymic bipolar disorder. In addition, the effect of galantamine on clinical measures of functioning and psychopathology was assessed. METHOD: This study was a randomized double-blind, placebo-controlled, parallel design examining the impact of galantamine augmentation on cognition and other clinical measures in 30 patients during the course of 3 months. Sixteen subjects who completed baseline and follow-up second neuropsychological testing were evaluable (10 with galantamine and 6 with placebo). RESULTS: The galantamine group showed improved performance on the California Verbal Learning Test total learning and the placebo group showed improved performance on the 2 Delis-Kaplan Executive Functioning System trail-making conditions and category fluency. CONCLUSIONS: Episodic memory performance was improved in the galantamine treatment group but did not improve in the placebo group. In contrast, performance on 2 of the processing speed measures showed significant improvement in the placebo condition, whereas that of the patients treated with galantamine did not improve. Galantamine may thus have specific benefits for episodic memory, but not processing speed, in patients with cognitive impairment as part of bipolar disorder.

Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study.

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.