Olanzapine/Fluoxetine Combination vs. Fluoxetine Monotherapy in Treatment-Resistant Depression
the MPR take:
An article published in the journal Neuropsychopharmacology reports on a study comparing the safety and efficacy of olanzapine/fluoxetine combination therapy (OFC) vs. fluoxetine monotherapy in patients with treatment-resistant major depressive disorder (MDD). Previous clinical trials have shown that the combination of olanzapine + fluoxetine produces a synergistic increase in norepinephrine and dopamine release in the prefrontal cortex compared with either component alone, as well as an increase in serotonin. In this study, patients with treatment-resistant MDD were treated for 6–8 weeks with OFC, followed by a 12-week stabilization period on OFC. 444 stabilized patients were then randomized to receive either OFC or fluoxetine monotherapy for another 27 weeks. The primary efficacy outcome was time-to-relapse (defined as 50% increase in Montgomery-Asberg Depression Rating Scale score with Clinical Global Impressions-Severity of Depression score of >4; hospitalization for depression or suicidality; or discontinuation for lack of efficacy or worsening of depression or suicidality). In the OFC-treated group, time-to-relapse was significantly longer than in the fluoxetine-treated group (p<0.001). With regards to adverse effects, no significant differences were seen between the two groups in extrapyramidal symptoms, however, weight gain and other metabolic changes were significantly greater in patients treated with OFC. Researchers believe this to be the first study that supports continued use of second-generation antipsychotics beyond the stabilization period; however, because of potential metabolic changes, the benefits and risks of long-term therapy need to be assessed on an individual basis.
This study assessed prevention of relapse in patients with treatment-resistant depression (TRD) taking olanzapine/fluoxetine combination (OFC). Patients with major depressive disorder (MDD) who failed to satisfactorily respond to 2 different antidepressants for 6 weeks within the current MDD episode were acutely treated for 6–8 weeks, followed by stabilization (12 weeks) on OFC.
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