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

• Sponsor: Maurizio Fava, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01464229
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 32
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Iloperidone; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled Crossover Study of Iloperidone Augmentation of SSRIs for Residual Anger and Irritability in Major Depressive Disorder
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Iloperidone addition to SSRI antidepressant	Drug: Iloperidone; Iloperidone 1-8 mg for 4 weeks
Placebo Comparator: Placebo addition to standard SSRI antidepressant	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. SQ Anger/Hostility Scale [9 weeks]

   Of the 20 patients randomized, data was analyzed for 13 completers. Symptom Questionnaire (SQ) Anger/Hostility Scale; this is a 23-item subscale of the 92-item Symptom Questionnaire. This score ranges from 0 to 23; higher values represent higher anger and hostility.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

• 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Maurizio Fava, MD
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Maurizio Fava, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Maurizio Fava, MD, Executive Vice Chair, Department of Psychiatry, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01464229
• Other Study ID Numbers: 2011P002043
• First Posted: Nov 3, 2011
• Last Update Posted: Apr 11, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Iloperidone

Study Results

Participant Flow

Arm/Group Title	Iloperidone, Then Placebo	Placebo, Then Iloperidone
Arm/Group Description	Iloperidone (1-8 mg) for 4 weeks, then placebo for 4 weeks; in addition to standard SSRI antidepressant	Placebo: Placebo for 4 weeks, then iloperidone for 4 weeks; in addition to standard SSRI antidepressant
Period Title: Overall Study
STARTED	10	10
COMPLETED	5	8
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Iloperidone, Then Placebo	Placebo, Then Iloperidone	Total
Arm/Group Description	Iloperidone: Iloperidone 1-8 mg for 4 weeks then placebo for 4 weeks, in addition to SSRI antidepressant	Placebo: Placebo for 4 weeks then iloperidone for 4 weeks; addition to standard SSRI antidepressant	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Sex/Gender, Customized (Count of Participants)
Females	6 60%	8 80%	14 70%
Males	4 40%	2 20%	6 30%

Outcome Measures

1. Primary Outcome

Title	SQ Anger/Hostility Scale
Description	Of the 20 patients randomized, data was analyzed for 13 completers. Symptom Questionnaire (SQ) Anger/Hostility Scale; this is a 23-item subscale of the 92-item Symptom Questionnaire. This score ranges from 0 to 23; higher values represent higher anger and hostility.
Time Frame	9 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Iloperidone, Then Placebo	Placebo, Then Iloperidone
Arm/Group Description	Iloperidone: Iloperidone 1-8 mg for 4 weeks then placebo for 4 weeks; addition to SSRI antidepressant	Placebo: Placebo for 4 weeks then iloperidone for 4 weeks; addition to standard SSRI antidepressant
Measure Participants	5	8
Iloperidone	4.8 (4.3)	8 (6.2)
Placebo	6.7 (5.8)	7.5 (7.2)

Adverse Events

Arm/Group Title	Iloperidone		Placebo
Arm/Group Description
All Cause Mortality
	Iloperidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Iloperidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		0/13 (0%)
Cardiac disorders
Palpitations	1/13 (7.7%)	1	0/13 (0%)	0
General disorders
Increased Irritability	1/13 (7.7%)	1	0/13 (0%)	0
Other (Not Including Serious) Adverse Events
	Iloperidone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		5/13 (38.5%)
Gastrointestinal disorders
Nausea	2/13 (15.4%)		1/13 (7.7%)
Cramping	1/13 (7.7%)		0/13 (0%)
Nervous system disorders
Somnolence	2/13 (15.4%)		2/13 (15.4%)
Headaches	2/13 (15.4%)		1/13 (7.7%)
Skin and subcutaneous tissue disorders
Dry Mouth	6/13 (46.2%)		1/13 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.