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

NCT ID: NCT01464229

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-12-31

Brief 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.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Iloperidone addition to SSRI antidepressant

Group Type: EXPERIMENTAL

Iloperidone

Intervention Type: DRUG

Iloperidone 1-8 mg for 4 weeks

Placebo addition to standard SSRI antidepressant

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Iloperidone

Iloperidone 1-8 mg for 4 weeks

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Maurizio Fava, MD

OTHER

Sponsor Role: lead

Responsible Party

Maurizio Fava, MD

Executive Vice Chair, Department of Psychiatry

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Maurizio Fava, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Ionescu DF, Fava M, Kim DJ, Baer L, Shelton RC, Cusin C. A placebo-controlled crossover study of iloperidone augmentation for residual anger and irritability in major depressive disorder. Ther Adv Psychopharmacol. 2016 Feb;6(1):4-12. doi: 10.1177/2045125315618621.

Reference Type: RESULT

PMID: 26913173 (View on PubMed)

Other Identifiers

2011P002043

Identifier Type: -

Identifier Source: org_study_id