Olanzapine plus fluoxetine reduce depressive symptoms faster than either drug alone in people with treatment resistant depression

摘要

Treatment resistant depression (TRD) is a difficult dilemma for the clinician. When a patient has failed to adequately respond to monotherapy trials of two or more antidepressants the evidence base for treatment becomes scant and clinicians' opinions on what treatment strategy to pursue start to diverge. Combination therapies typically use one antidepressant agent together with an agent from a different pharmacological class. The combination of an atypical antipsychotic with an antidepressant in TRD has been demonstrated to be useful and has a plausible pharmacological basis.In the trial by Shelton ef a/ the olanzapine/fluoxetine combination (OFC) did not differ significantly at endpoint from other treatment arms on the primary outcome measure, suggesting that OFC was no more useful than monotherapy with olanzapine, fluoxetine, or nortriptyline for the treatment of TRD. People treated with OFC improved more rapidly than those in other treatment arms, with OFC superior to olanzapine monotherapy from weeks 2 to 4 and at week 7, OFC superior to fluoxetine from weeks 2 to 5 and OFC superior to nortriptyline from weeks 1 to 4.It is still to be determined whether the efficacy of OFC, demonstrated in other trials,can be generalised to other atypical antipsychotic antidepressant combinations. Clinical profiles suggesting response to this strategy require definition. The significance of the more rapid onset of antidepressant action of OFC compared to other treatment arms, and the subsequent equivalence of the four treatment arms at the eight week study endpoint is unclear. The small effect sizes overall may still reflect low response rates in refractory populations, yet may result in significant benefits for individuals. In situations of multiple treatment failures, a sequential use of validated options is indicated.