Importance of the field: Although a range of antidepressant medications are available, a substantial number of patients either do not respond adequately to these or are unable to tolerate their adverse effects. A treatment strategy that has gathered substantial empirical support is the use of second generation antipsychotic agents (SGAs) in combination with antidepressants for treatment-resistant nonpsychotic depression (TRD) or major depressive disorder (MDD) inadequately responsive to antidepressants. Aripiprazole, olanzapine and quetiapine each have indications that involve MDD. Growing evidence indicates that quetiapine, evaluated as the extended release formulation, is efficacious as monotherapy for nonpsychotic MDD.
Areas covered in this review: The pharmacological rationale for using SGAs in MDD, randomized, placebo-controlled data on individual SGAs in treatment of MDD and the emerging role of SGAs in the management of MDD.
What the reader will gain: A balanced overview of the evidence supporting the use of newer SGAs in MDD.
Take home message: SGAs will have an increasingly important role in treatment of MDD, especially as augmentation agents. Further research is needed to clarify their efficacy and safety profiles, especially compared with other strategies for TRD.