Augmentation Treatments with Second-generation Antipsychotics to Antidepressants in Treatment-resistant Depression

Various classes of antidepressants have been used in the treatment of major depressive disorder (MDD); however, the efficacy of these treatments remains uncertain. A number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that approximately 30 % of MDD patients remit following antidepressant treatment, leaving approximately 70 % of patients with significant residual symptoms. In these latter patients with what is considered treatment-resistant MDD, typical antipsychotics have sometimes been administered in order to augment the antidepressant effects but safety and tolerability concerns significantly reduce their usage in MDD patients. The advent of second-generation antipsychotics (SGAs), which have diverse pharmacodynamic profiles relative to antidepressants, has dramatically increased the usage of such drugs for patients with MDD. Recently, SGAs such as aripiprazole, quetiapine and olanzapine in combination with fluoxetine have been approved for the treatment of MDD, especially in the case of treatment resistance. This article reviews the efficacy and tolerability of SGA augmentation when added to antidepressant therapy for treatment-resistant MDD patients in acute phase studies published to date.