Comparison of fluoxetine, olanzapine, and combined fluoxetine plus olanzapine initial therapy of bipolar type I and type II major depression - Lack of manic induction

ArticleinJournal of Affective Disorders 87(1):121-30 · July 2005with10 Reads
Impact Factor: 3.38 · DOI: 10.1016/j.jad.2005.02.018 · Source: PubMed


    Current guidelines for the initial treatment of bipolar type I (BP I) and bipolar type II (BP II) major depressive episode (MDE) recommend avoiding the use of antidepressant drugs due to concerns over drug-induced manic switch episodes. However, recent evidence suggests that the manic switch rate during SSRI therapy of BP MDE may be lower than previously thought. This preliminary, placebo-controlled study examines the relative rates of treatment-emergent manic symptoms during fluoxetine monotherapy, olanzapine monotherapy, and combined fluoxetine plus olanzapine therapy of BP I and BP II MDE.
    32 BP I and 2 BP II MDE patients were randomized to receive double-blind therapy with fluoxetine monotherapy 10-30 mg daily, olanzapine monotherapy 5-20 mg daily, combined therapy with fluoxetine 10-40 mg plus olanzapine 5-15 mg daily, or placebo for up to 8 weeks. Outcome measures included the 17-item HAM-D, 17-item HAM-D "atypical" symptom profile (HAM-D 17-R), 28 item HAM-D, Montgomery-Asberg Depression Rating Scale (MADRS), and the Young Mania Rating (YMR) scale.
    There were significant reductions over time in mean HAM-D 28 and MADRS ratings for all treatment groups (p<0.006). However, there were no differences among treatment conditions (p=ns). There was no significant increase in YMR scores over time in any treatment group. In contrast, there was a significant reduction in the mean YMR score in the fluoxetine-treated patients over time (p=0.008). No patient met DSM IV criteria for a manic episode.
    Cohort sizes were limited and the study was not powered to detect statistical differences in efficacy or mania symptoms among treatment conditions. The dose of fluoxetine was modest and the treatment duration was limited to 8 weeks.
    These observations support earlier findings of a low manic switch rate during fluoxetine monotherapy of BP I and BP II MDE, and suggest that fluoxetine may be a safe initial treatment of BP MDE alone or in combination with olanzapine.