Iloperidone is an atypical antipsychotic drug, FDA-approved for the acute treatment of schizophrenia in adults in 2009 (Marino et al., 2010); moreover, some of its pharmacological features seem to be very promising in treating symptoms like anger and anxiety (Fava et al., 1997; Wang et al., 2010). The investigators therefore feel that an adequately sized, well powered, double-blind, placebo-controlled, randomized, cross-over study of iloperidone augmentation of SSRIs among MDD outpatients in partial remission with residual anger and irritability is warranted at this point to evaluate its efficacy, safety and tolerability on residual anger, irritability and depressive symptoms.