Iloperidone Augmentation of SSRIs for Patients With Major Depressive Disorder With Residual Anger and Irritability

Inclusion Criteria: * Written informed consent. * Men or women ages 18-65 years old. * Current Major Depressive Episode in partial remission based on the Structured Clinical Interview for DSM IV-Axis I Disorders (SCID I/P) and a HAM-D-17 score between 9 and 15. * Current treatment with a selective serotonin reuptake inhibitor (SSRI) other than paroxetine or fluoxetine for at least three months, at a stable dose for the past 4 weeks, and more than 50% but less than 75% improvement on the current antidepressant, as determined by the MGH Antidepressant Treatment Response Questionnaire (ATRQ). * Score \> 8 on the Anger/Hostility Scale of the Symptom Questionnaire both at screen and baseline. Exclusion Criteria: * The following DSM-IV diagnoses: 1) organic mental disorders; 2) substance use disorders, including alcohol, active within the last 3 months; 3) schizophrenia; 4) delusional disorder; 5) psychotic disorders not elsewhere classified; 6) bipolar disorder; and 9) antisocial personality disorder; 10) dementia. * Current, serious suicidal or homicidal risk. * Pregnancy or breast-feeding. * Serious, unstable medical illness including cardiovascular, kidney, liver, neurological and endocrine disorders. * Congenital long QT syndrome or a QTc \> 450 ms. * History of cardiac arrhythmias. * Electroconvulsive therapy (ECT) within the 6 months preceding baseline. * Concomitant use of buspirone, fluoxetine, paroxetine, any psychostimulant, modafinil, other antipsychotic drugs, or anticonvulsants (although stable doses of benzodiazepines and hypnotics are allowed) (see Concomitant Therapy).