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WPC: Olanzapine-Fluoxetine for Treatment-Resistant Depression By Bruce Sylvester Special to DG News YOKOHAMA, JAPAN -- September 2, 2002 -- Olanzapine-fluoxetine combination (OFC) therapy leads to improvement in depressive symptoms with sustained efficacy over eight weeks, and demonstrates greater reduction in depressive symptoms than either drug as monotherapy. These findings were reported at the World Congress of Psychiatry in Yokohama. "Current antidepressant treatments do not help every patient with depression," the authors wrote. "Up to 30 percent of patients with major depressive disorder (MDD) are resistant to conventional antidepressant treatment. Subsequent medical therapy may include combinations of antidepressants or various augmentation strategies, such as a combined antidepressant-antipsychotic approach. Atypical antipsychotic agents, such as olanzapine, cause fewer extrapyramidal adverse effects than conventional antipsychotics, and may be an advantageous augmentation strategy for treatment-resistant depression (TRD)." "The purpose of this meta-analysis was to compare the efficacy of olanzapine/fluoxetine combination (OFC) with component (olanzapine and fluoxetine) monotherapies in TRD (defined as failure to respond to adequate trials of two classes of antidepressants) using data pooled from two studies," the authors added. The investigators performed a meta-analysis of two (eight-week and 12-week) double-blind studies involving 797 subjects diagnosed with nonpsychotic, unipolar, treatment-resistant major depression. Montgomery-Asberg Depression Rating Scale (MADRS) was used at baseline and endpoint to measure efficacy. OFC patients achieved significantly greater total score improvement (-7.31) at Week 1 than olanzapine subjects (-5.18, p=0.013) or fluoxetine subjects (-5.26, p=0.004). This significant effect abided during the eight weeks of treatment. (Endpoint: OFC -11.60, olanzapine -7.55, p<0.001; fluoxetine, -8.73, p<0.001). OFC patients had a significantly higher rate of response as a group at endpoint (eight weeks) than olanzapine (37.3 percent vs. 21.1 percent) OFC subjects showed a significantly greater endpoint remission rate than olanzapine or fluoxetine (OFC 24.9 percent, olanzapine 13.1 percent, fluoxetine 15.2 percent). The authors concluded that, "OFC had robust onset of action within seven days of treatment and maintained treatment effect throughout eight weeks. OFC showed significantly greater improvement in depressive symptoms than olanzapine or fluoxetine monotherapies from weeks one through eight. OFC had a significantly greater response rate that olanzapine, and a significantly greater remission rate than olanzapine or fluoxetine." The study was supported by Lilly Research Laboratories. E-mail this page to a friend or colleague! To print, use this version