Olanzapine and fluoxetine combined as therapy for treatment-resistant depression: a systematic review

Objective: we conducted a systematic review to evaluate the evidence for the efficacy and safety of olanzapinefluoxetine combined (OFC) in patients with treatment-resistant depression (TRD). Material and methods: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and LillyTrials.com were searched (28 February 2014) using terms related to TRD and OFC (no language restrictions). All prospective studies of OFC treatment of TRD were included. Results: we included 16 studies (5 meta-analyses, 3 pooled analyses, 7 randomized controlled trials [RCTs], 1 nonrandomized, open-label trial); unpublished data of open-label extensions were available for 4 RCTs. The definition of TRD varied; most studies defined TRD as response failure after 2 antidepressant trials of4 weeks. All RCTs compared OFC with fluoxetine. Treatment duration was 4 12 weeks in RCTs, and 8 76 weeks in open-label studies. Depressive symptoms improved with OFC treatment in all studies; improvement was generally greater and occurred earlier than with fluoxetine and was sustained during longer-term treatment. Response (27.5%-80%) and remission (16.9%-73.3%) rates were generally greater than with fluoxetine. Weight gain and changes in metabolic parameters were generally more common in patients treated with OFC than with fluoxetine. Other adverse events and discontinuation rates were similar to those seen with fluoxetine. Conclusions: evidence from prospective studies supports the efficacy of OFC in the treatment of TRD, which is sustained with longer-term treatment. However, there may be a greater risk of weight gain and changes in metabolic parameters. Physicians may consider OFC as treatment for TRD, provided the risks of weight gain and metabolic changes are actively managed.