The outcome of treatment for major depression is suboptimal. Only a minority of patients (<30%) achieve remission with the first antidepressant, and most relapse. Each subsequent treatment trial yields even lower rates of remission. Psychotherapy, similarly, results in a 30% remission rate and a 50% improvement in 50% of depressed patients. Between 15% and 30% of depressed patients have a chronic course of illness despite adequate treatment trials. There is, therefore, a well-established need for new approaches for depressed patients who have not responded well to commonly used antidepressant treatments.

The development of second-generation antipsychotic medications with arguably more benign side effect profiles has led to a renewed interest in their use for the treatment of depression. …