Iloperidone Augmentation of SSRIs for Patients With Major Depressive Disorder With Residual Anger and Irritability
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Iloperidone; Placebo
Intervention description: Iloperidone 1-8 mg for 4 weeks; Placebo
Intervention MeSH terms: Iloperidone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      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.

      Main hypothesis: Adults with MDD in partial remission, who are experiencing residual symptoms
      of anger and irritability, assigned to treatment with iloperidone will demonstrate a
      significantly greater reduction in the total score of the Anger/Hostility Scale of the
      Symptom Questionnaire from baseline to endpoint than those assigned to placebo using the
      cross-over design.
    

Eligibility criteria:

        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).