Major Depressive Disorder
Conditions
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.
Interventions
DRUGIloperidone
Iloperidone 1-8 mg for 4 weeks
DRUGPlacebo
Placebo
Sponsors
Novartis Pharmaceuticals
Maurizio Fava, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iloperidone, Then Placebo Iloperidone: Iloperidone 1-8 mg for 4 weeks then placebo for 4 weeks, in addition to SSRI antidepressant | 10 |
| Placebo, Then Iloperidone Placebo: Placebo for 4 weeks then iloperidone for 4 weeks; addition to standard SSRI antidepressant | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Iloperidone, Then Placebo | Placebo, Then Iloperidone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 20 Participants |
| Sex/Gender, Customized Females | 6 Participants | 8 Participants | 14 Participants |
| Sex/Gender, Customized Males | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 5 / 13 |
| serious Total, serious adverse events | 2 / 13 | 0 / 13 |
Outcome results
Primary
SQ Anger/Hostility Scale
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Iloperidone, Then Placebo | SQ Anger/Hostility Scale | Iloperidone | 4.8 Score on Anger/Hostility Scale | Standard Deviation 4.3 |
| Iloperidone, Then Placebo | SQ Anger/Hostility Scale | Placebo | 6.7 Score on Anger/Hostility Scale | Standard Deviation 5.8 |
| Placebo, Then Iloperidone | SQ Anger/Hostility Scale | Iloperidone | 8 Score on Anger/Hostility Scale | Standard Deviation 6.2 |
| Placebo, Then Iloperidone | SQ Anger/Hostility Scale | Placebo | 7.5 Score on Anger/Hostility Scale | Standard Deviation 7.2 |