Treatment resistance is frequently encountered during the
long-term care of patients with major depression. A number of 'next step' therapeutic options exist in such cases, including switching to an alternative
antidepressant, combining
antidepressants from different pharmacological classes, adding evidence-supported psychotherapies to ongoing
antidepressant treatment and augmentation with a nonantidepressant
drug. Augmenting
antidepressants with atypical
antipsychotic drugs has generated considerable clinical interest. Three atypical
antipsychotics (
aripiprazole,
quetiapine and
olanzapine) have received regulatory approval for adjunctive use with
antidepressants for treatment-resistant major depression (TRD) in adults.
Symbyax (
olanzapine-fluoxetine combination or OFC), the combination of
olanzapine and the
selective serotonin-reuptake inhibitor fluoxetine, is also approved for this indication. The short-term effectiveness of OFC for TRD is supported by results of five published randomized, controlled, acute-phase studies of generally similar design. In each study, OFC was associated with rapid reduction in depressive symptoms. In two studies, significantly greater improvement in depressive symptoms occurred in OFC-treated patients at study end point compared with those who received
antidepressant monotherapy. These effects appeared to be strongest in cases where
antidepressant failure was established during the current depressive episode. Although OFC was well-tolerated, increases in
body weight and
prolactin concentration were greater with OFC than
antidepressant monotherapy, and were similar to
olanzapine monotherapy. Increases in random total
cholesterol levels were greatest for OFC, and were significantly greater than those of
olanzapine and
antidepressant monotherapy. The long-term efficacy and tolerability of OFC for TRD has not been investigated, and the comparative effectiveness of OFC versus other next-step options is unknown. As such, the exact place of OFC among the available therapeutic options for TRD is not fully understood at this time.