Use of second generation antipsychotics for treatment-resistant major depressive disorder

Many of the second generation antipsychotics (SGAs) have been studied as adjunctive agents in the management of treatment-resistant major depressive disorder. Two have also been examined for use as monotherapy for depression. Currently, aripiprazole, olanzapine (in combination with fluoxetine), and quetiapine XR are approved by the FDA for use as adjunctive agents in the treatment of major depressive disorder, and no SGAs are FDA-approved as monotherapy for the disorder. This article reviews the available evidence regarding the use of SGAs in patients with treatment-resistant major depressive disorder and the subsequent role for these agents based on this evidence. There is evidence that aripiprazole, quetiapine, olanzapine, and risperidone can be effective in improving depressive symptoms when added to antidepressant therapy, but the benefits have to be weighed against their risk of producing serious adverse effects.