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Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy

Primary Purpose

Major Depressive Disorder, Irritability

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Brexpiprazole

About this trial

This is an interventional treatment trial for Major Depressive Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Main selection criteria at screening visit:

The patient has a Major Depressive Episode (MDE) associated to Major Depressive Disorder (MDD) diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR™). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI)
The patient has an inadequate response to at least one antidepressant treatment (including the treatment the patient is taking at screening) in the current MDE, as documented by self-report as less than a pre-defined percentage response on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ).
Pre-defined MADRS total score
Pre-defined CGI-S total score
The patient has had the current MDE for ≥10 weeks
The patient is receiving a SSRI or SNRI antidepressant treatment for ≥6 weeks, at same dosage for ≥2 weeks
Pre-defined Inventory of Depressive Symptomatology - Clinician-Rated - 30 items (IDS-C 30) Item 6 Mood (irritable) score

Main inclusion criteria at baseline visit:

The patient still fulfils DSM-IV-TR™ criteria for MDE
Pre-defined MADRS total score
Pre-defined CGI-I (Lead-in period) score
The patient received the same SSRI or SNRI antidepressant treatment at adequate doses during the entire lead-in period
The patient has less than a pre-defined percentage decrease in MADRS score at the end of the lead-in period as compared to the screening visit
The patient still has the pre-defined IDS-C 30 Item 6 Mood (Irritable) score

Exclusion Criteria:

The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the principal diagnosis, other than MDD. All anxiety disorders, impulse-control disorders such as intermittent explosive disorder, as well as non-suicidal self-injury are not excluded diagnoses as far as they are not considered as principal diagnosis.
The patient has a current Axis II (DSM-IV-TR™) diagnosis of antisocial, borderline, paranoid, schizoid, schizotypical, or histrionic personality disorder.
The patient has experienced/experiences hallucinations, delusions, or any psychotic symptomatology in the current MDE.
The patient, in the opinion of the investigator or based on C-SSRS rating, is at significant risk of suicide.
The patient has started formal cognitive or behavioural therapy or systematic psychotherapy within 6 weeks prior to screening, or plans to start such therapy during the study. Any ongoing formal psychotherapy initiated more than 6 weeks prior to screening should be continued with the same methodology and at the same frequency and intensity during the entire study.
The patient has a current diagnosis or history of substance abuse or dependence (excluding nicotine or caffeine) or alcohol abuse or dependence (DSM-IV-TR™ criteria) <6 months prior to the Screening Visit.
The patient reports adjunctive treatment with an antipsychotic medication together with an antidepressant for 3 weeks or more during the current MDE.
The patient has received electroconvulsive therapy (ECT) <6 months prior to the Screening Visit or at any time during the current MDE (if its duration is longer than 6 months).
The patient has had vagus nerve stimulation or a deep brain stimulation device implanted for the management of depression.

Other inclusion and exclusion criteria may apply.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Brexpiprazole

Arm Description

Brexpiprazole adjunct to open-label commercially available Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI) antidepressant treatment (ADT)

Outcomes

Primary Outcome Measures

Change From Baseline to Week 6 in SIS Total Score

Change From Baseline to Week 6 in SIS Item 1 Score

The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS item 1 assess how much the patient has suffered from irritability in the past week. The SIS item 1 ranged from 0 to 10 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in IDS-C30 Item 6 Score

The 30-item Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C30) is a clinician-rated scale designed to assess the severity of depressive symptoms. The IDS-C30 item 6 measures mood (irritable) and is rated on a 4-point anchored scale from 0 (least severe) to 3 (most severe) with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in Delay Discounting - Log-transformed MCQ Scores

The Monetary Choice Questionnaire (MCQ) is a patient-completed questionnaire designed to measure delay discounting, an index of impulsive behaviour. The MCQ consists of 27 choices between immediate and delayed rewards. The patients choose repeatedly between two hypothetical sums of money: a smaller amount now or a larger amount in the future (for example, ''Would you prefer $27 today or $50 in 21 days?"). The answers provide an estimate of the patient's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicate impulsivity. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in BIS-11 Total Score

The Barratt Impulsiveness Scale, Version 11 (BIS-11) is a patient-rated scale designed to assess impulsive personality traits. The BIS-11 consists of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The total score ranges from 30 to 120 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in KSQ Anger-hostility Subscore

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ anger-hostility subscale score ranges from 0 to 23 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Shift From Baseline to Week 6 in Anger Attacks (AAQ)

The Anger Attacks Questionnaire (AAQ) is a patient-rated scale designed to assess the presence of anger attacks over a period of time. The AAQ consists of 7 items. Patients are classified as having anger attacks when exhibiting the following 4 criteria: 1) irritability, 2) overreaction to minor annoyances, 3) occurrence of anger attacks (at least one of which occurred within the period), and 4) experienced 4 or more specific symptoms during at least one of the attacks. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in IDS-C30 Total Score

The 30-item Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C30) is a clinician-rated scale designed to assess the severity of depressive symptoms. The IDS-C30 consists of 30 items assessing the symptoms of depression, as well as commonly associated symptoms (for example, anxiety, irritability), and topics relevant to melancholic or atypical features; the patient rates only one of the 2 items assessing appetite (decreased or increased), and only one of the 2 items assessing weight (loss or gain). Each of the items is rated on a 4-point anchored scale from 0 (least severe) to 3 (most severe). The total score is the sum of the 28 scored items, and ranges from 0 to 84, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in KSQ Depression Subscore

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ depression subscale score ranges from 0 to 23, with higher values indicating worse outcome . As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in MADRS Total Score

Change From Baseline to Week 6 in CPFQ Total Score

The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a patient-rated scale designed to assess cognitive and executive dysfunction including symptoms of fatigue in mood and anxiety disorders. The CPFQ consists of 7 items, each rated on a scale from 1 (greater than normal functioning) to 6 (poorer than normal functioning). The total score of the 7 items ranges from 7 to 42, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in CGI-S Score

The Clinical Global Impression severity of illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

CGI-I Score at Week 6

The Clinical Global Impression - global improvement CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in KSQ Total Score

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ consists of 92 items which form the basis for the four subscales: depression, anxiety, anger-hostility, and somatic; of which 68 items indicate symptoms (symptom subscales) and 24 items are antonyms of some of the symptoms and indicate well-being (well-being subscales). A "yes" or "true" response on the symptom subscales scores 1, and a "no" or "false" on the well-being subscales scores 1. The maximum score for each symptom subscale is 17, and the maximum score for each well-being subscale is 6. The score of each subscale ranges from 0 to 23 (the sum of the symptom subscale and the well-being subscale). A higher score indicates more distress. The total score ranges from 0 to 92. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in Delay Discounting - Log-transformed EDT DPDT Scores

DPDT consists of approximately 110 choices between an immediate reward or a higher delayed reward, and between an immediate reward or a higher reward that only comes with a certain probability. The tasks are scored independently of each other and do not yield a total score. There will be two derived variables from this task; a delayed discounting rate and a probability discounting rate. The delay discounting value takes values from 0 and up, a higher delay discounting value indicates greater impulsivity. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in Delay Discounting - EDT DRT Score

DRT consists of 60 choices between an immediate reward or a higher delayed reward. The number of impulsive choices will be a continuous variable estimated from how many immediate choices based on 60 possible. The number ranges between 0 and 60, with a higher value indicating more impulsivity. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Week 6 to Week 10 in SIS Total Score

The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS consists of 7 subscales assessing irritability, frustration, edginess/impatience/overreaction, moodiness, anger with self, anger with others, and temper. The patient rates the extent to which they have suffered from these symptoms. Each subscale has verbal descriptors (not at all, mildly, moderately, markedly, and extremely) as well as numerical scores from 0 (not at all) to 10 (extremely) that provide more precise levels of the verbal descriptors. One additional question assesses number of days impaired by irritability over the period. The subscales are summarised to give the total score which ranges from 0 to 70, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Week 6 to Week 10 in SIS Item 1 Score

The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS item 1 assess how much the patient has suffered from irritability in the past week, using verbal descriptors (not at all, mildly, moderately, markedly, and extremely) as well as numerical scores from 0 (not at all) to 10 (extremely) that provide more precise levels of the verbal descriptors. The SIS item 1 ranged from 0 to 10 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Week 6 to Week 10 in Delay Discounting - MCQ Scores

Change From Week 6 to Week 10 in BIS-11 Total Score

The Barratt Impulsiveness Scale, Version 11 (BIS-11) is a patient-rated scale designed to assess impulsive personality traits. The BIS-11 consists of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provide information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranges from 30 to 120 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Week 6 to Week 10 in KSQ Anger-hostility Subscore

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ anger-hostility subscale score ranges from 0 to 23 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Week 6 to Week 10 in KSQ Depression Subscore

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ depression subscale score ranges from 0 to 23, with higher values indicating worse outcome . As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Week 6 to Week 10 in CGI-S Score

Change From Baseline to Week 6 in MADRS Total Score in Patients With a Pre-defined Baseline BIS-11 Total Score

The Montgomery and Åsberg Depression Rating Scale (MADRS) is a 10-item rating scale designed to assess the severity of the symptoms in depressive illness and to be sensitive to treatment effects. Symptoms are rated on a 7-point scale from 0 (no symptom) to 6 (severe symptom). The total score of the 10 items ranges from 0 to 60, with higher values indicating worse outcome. Subgroup analyses were performed for the change from Baseline to Week 6 in MADRS total score based on the patients' BIS-11 total score at Baseline. The subgroups denoted BIS-11_HIGH had a BIS-11 total score at Baseline ≥median at baseline and the subgroups denoted BIS-11_LOW had a BIS-11 total score <median at baseline. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Change From Baseline to Week 6 in CGI-S Score in Patients With a Pre-defined Baseline BIS-11 Total Score

The subgroups denoted BIS-11_HIGH had a BIS-11 total score at Baseline ≥median at baseline and the subgroups denoted BIS-11_LOW had a BIS-11 total score <median at baseline. The Clinical Global Impression severity of illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

CGI-I Score at Week 6 Patients With a Pre-defined Baseline BIS-11 Total Score

The subgroups denoted BIS-11_HIGH had a BIS-11 total score at Baseline ≥median at baseline and the subgroups denoted BIS-11_LOW had a BIS-11 total score <median at baseline. The Clinical Global Impression - global improvement CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Secondary Outcome Measures

Full Information

NCT ID

NCT01942785

First Posted

September 11, 2013

Last Updated

February 16, 2016

Sponsor

H. Lundbeck A/S

1. Study Identification

Unique Protocol Identification Number

NCT01942785

Brief Title

Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy

Official Title

Interventional, Open-label, Flexible-dose, Exploratory Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

October 2013 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lundbeck A/S

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

To explore the anti-impulsive and anti-aggressive properties of brexpiprazole in a naturalistic setting of depressed patients with irritability.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder, Irritability

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

55 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Brexpiprazole

Arm Type

Experimental

Arm Description

Brexpiprazole adjunct to open-label commercially available Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI) antidepressant treatment (ADT)

Intervention Type

Drug

Intervention Name(s)

Brexpiprazole

Intervention Description

2-3 mg/day, once daily dose, tablets, for oral use. The patients received 1mg/day brexpiprazole during Week 1 and 2mg/day during Week 2 (up-titration) and from Weeks 3 to 6 they received 3mg/day; depending on tolerability the dose could be reduced to 2mg/day based on the investigator's judgement.

Primary Outcome Measure Information:

Title

Change From Baseline to Week 6 in SIS Total Score

Description

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in SIS Item 1 Score

Description

The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS item 1 assess how much the patient has suffered from irritability in the past week. The SIS item 1 ranged from 0 to 10 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in IDS-C30 Item 6 Score

Description

The 30-item Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C30) is a clinician-rated scale designed to assess the severity of depressive symptoms. The IDS-C30 item 6 measures mood (irritable) and is rated on a 4-point anchored scale from 0 (least severe) to 3 (most severe) with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in Delay Discounting - Log-transformed MCQ Scores

Description

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in BIS-11 Total Score

Description

The Barratt Impulsiveness Scale, Version 11 (BIS-11) is a patient-rated scale designed to assess impulsive personality traits. The BIS-11 consists of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The total score ranges from 30 to 120 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in KSQ Anger-hostility Subscore

Description

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ anger-hostility subscale score ranges from 0 to 23 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Baseline and Week 6

Title

Shift From Baseline to Week 6 in Anger Attacks (AAQ)

Description

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in IDS-C30 Total Score

Description

The 30-item Inventory of Depressive Symptomatology - Clinician-Rated (IDS-C30) is a clinician-rated scale designed to assess the severity of depressive symptoms. The IDS-C30 consists of 30 items assessing the symptoms of depression, as well as commonly associated symptoms (for example, anxiety, irritability), and topics relevant to melancholic or atypical features; the patient rates only one of the 2 items assessing appetite (decreased or increased), and only one of the 2 items assessing weight (loss or gain). Each of the items is rated on a 4-point anchored scale from 0 (least severe) to 3 (most severe). The total score is the sum of the 28 scored items, and ranges from 0 to 84, with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in KSQ Depression Subscore

Description

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ depression subscale score ranges from 0 to 23, with higher values indicating worse outcome . As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in MADRS Total Score

Description

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in CPFQ Total Score

Description

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in CGI-S Score

Description

Time Frame

Baseline and Week 6

Title

CGI-I Score at Week 6

Description

Time Frame

Week 6

Title

Change From Baseline to Week 6 in KSQ Total Score

Description

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ consists of 92 items which form the basis for the four subscales: depression, anxiety, anger-hostility, and somatic; of which 68 items indicate symptoms (symptom subscales) and 24 items are antonyms of some of the symptoms and indicate well-being (well-being subscales). A "yes" or "true" response on the symptom subscales scores 1, and a "no" or "false" on the well-being subscales scores 1. The maximum score for each symptom subscale is 17, and the maximum score for each well-being subscale is 6. The score of each subscale ranges from 0 to 23 (the sum of the symptom subscale and the well-being subscale). A higher score indicates more distress. The total score ranges from 0 to 92. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in Delay Discounting - Log-transformed EDT DPDT Scores

Description

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in Delay Discounting - EDT DRT Score

Description

Time Frame

Baseline and Week 6

Title

Change From Week 6 to Week 10 in SIS Total Score

Description

Time Frame

Week 6 and Week 10

Title

Change From Week 6 to Week 10 in SIS Item 1 Score

Description

The Sheehan Irritability Scale (SIS) is a patient-rated scale designed to measure irritability. The SIS item 1 assess how much the patient has suffered from irritability in the past week, using verbal descriptors (not at all, mildly, moderately, markedly, and extremely) as well as numerical scores from 0 (not at all) to 10 (extremely) that provide more precise levels of the verbal descriptors. The SIS item 1 ranged from 0 to 10 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Week 6 and Week 10

Title

Change From Week 6 to Week 10 in Delay Discounting - MCQ Scores

Description

Time Frame

Week 6 and Week 10

Title

Change From Week 6 to Week 10 in BIS-11 Total Score

Description

The Barratt Impulsiveness Scale, Version 11 (BIS-11) is a patient-rated scale designed to assess impulsive personality traits. The BIS-11 consists of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provide information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranges from 30 to 120 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Week 6 and Week 10

Title

Change From Week 6 to Week 10 in KSQ Anger-hostility Subscore

Description

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ anger-hostility subscale score ranges from 0 to 23 with higher values indicating worse outcome. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Week 6 and Week 10

Title

Change From Week 6 to Week 10 in KSQ Depression Subscore

Description

The Kellner Symptom Questionnaire (KSQ) is a patient-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility, and somatization. The KSQ depression subscale score ranges from 0 to 23, with higher values indicating worse outcome . As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Week 6 and Week 10

Title

Change From Week 6 to Week 10 in CGI-S Score

Description

Time Frame

Week 6 and Week 10

Title

Change From Baseline to Week 6 in MADRS Total Score in Patients With a Pre-defined Baseline BIS-11 Total Score

Description

Time Frame

Baseline and Week 6

Title

Change From Baseline to Week 6 in CGI-S Score in Patients With a Pre-defined Baseline BIS-11 Total Score

Description

Time Frame

Baseline and Week 6

Title

CGI-I Score at Week 6 Patients With a Pre-defined Baseline BIS-11 Total Score

Description

The subgroups denoted BIS-11_HIGH had a BIS-11 total score at Baseline ≥median at baseline and the subgroups denoted BIS-11_LOW had a BIS-11 total score <median at baseline. The Clinical Global Impression - global improvement CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. As this was an open-label exploratory study, all outcomes should be considered as exploratory outcomes.

Time Frame

Week 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Main selection criteria at screening visit: The patient has a Major Depressive Episode (MDE) associated to Major Depressive Disorder (MDD) diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR™). The current MDE should be confirmed using the Mini International Neuropsychiatric Interview (MINI) The patient has an inadequate response to at least one antidepressant treatment (including the treatment the patient is taking at screening) in the current MDE, as documented by self-report as less than a pre-defined percentage response on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ). Pre-defined MADRS total score Pre-defined CGI-S total score The patient has had the current MDE for ≥10 weeks The patient is receiving a SSRI or SNRI antidepressant treatment for ≥6 weeks, at same dosage for ≥2 weeks Pre-defined Inventory of Depressive Symptomatology - Clinician-Rated - 30 items (IDS-C 30) Item 6 Mood (irritable) score Main inclusion criteria at baseline visit: The patient still fulfils DSM-IV-TR™ criteria for MDE Pre-defined MADRS total score Pre-defined CGI-I (Lead-in period) score The patient received the same SSRI or SNRI antidepressant treatment at adequate doses during the entire lead-in period The patient has less than a pre-defined percentage decrease in MADRS score at the end of the lead-in period as compared to the screening visit The patient still has the pre-defined IDS-C 30 Item 6 Mood (Irritable) score Exclusion Criteria: The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the principal diagnosis, other than MDD. All anxiety disorders, impulse-control disorders such as intermittent explosive disorder, as well as non-suicidal self-injury are not excluded diagnoses as far as they are not considered as principal diagnosis. The patient has a current Axis II (DSM-IV-TR™) diagnosis of antisocial, borderline, paranoid, schizoid, schizotypical, or histrionic personality disorder. The patient has experienced/experiences hallucinations, delusions, or any psychotic symptomatology in the current MDE. The patient, in the opinion of the investigator or based on C-SSRS rating, is at significant risk of suicide. The patient has started formal cognitive or behavioural therapy or systematic psychotherapy within 6 weeks prior to screening, or plans to start such therapy during the study. Any ongoing formal psychotherapy initiated more than 6 weeks prior to screening should be continued with the same methodology and at the same frequency and intensity during the entire study. The patient has a current diagnosis or history of substance abuse or dependence (excluding nicotine or caffeine) or alcohol abuse or dependence (DSM-IV-TR™ criteria) <6 months prior to the Screening Visit. The patient reports adjunctive treatment with an antipsychotic medication together with an antidepressant for 3 weeks or more during the current MDE. The patient has received electroconvulsive therapy (ECT) <6 months prior to the Screening Visit or at any time during the current MDE (if its duration is longer than 6 months). The patient has had vagus nerve stimulation or a deep brain stimulation device implanted for the management of depression. Other inclusion and exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Email contact via H. Lundbeck A/S

Organizational Affiliation

LundbeckClinicalTrials@lundbeck.com

Official's Role

Study Director

Facility Information:

Facility Name

US015

City

Tucson

State/Province

Arizona

Country

United States

Facility Name

US019

City

Glendale

State/Province

California

Country

United States

Facility Name

US016

City

Oakland

State/Province

California

Country

United States

Facility Name

US014

City

San Diego

State/Province

California

Country

United States

Facility Name

US011

City

Denver

State/Province

Colorado

Country

United States

Facility Name

US018

City

Hallandale Beach

State/Province

Florida

Country

United States

Facility Name

US009

City

Jacksonville

State/Province

Florida

Country

United States

Facility Name

US005

City

Orlando

State/Province

Florida

Country

United States

Facility Name

US006

City

Gaithersburg

State/Province

Maryland

Country

United States

Facility Name

US012

City

Weymouth

State/Province

Massachusetts

Country

United States

Facility Name

US003

City

Jamaica

State/Province

New York

Country

United States

Facility Name

US001

City

Dayton

State/Province

Ohio

Country

United States

Facility Name

US007

City

Portland

State/Province

Oregon

Country

United States

Facility Name

US004

City

Memphis

State/Province

Tennessee

Country

United States

Facility Name

US002

City

Seattle

State/Province

Washington

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27379823

Citation

Fava M, Menard F, Davidsen CK, Baker RA. Adjunctive Brexpiprazole in Patients With Major Depressive Disorder and Irritability: An Exploratory Study. J Clin Psychiatry. 2016 Dec;77(12):1695-1701. doi: 10.4088/JCP.15m10470.

Results Reference

derived

Learn more about this trial

Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy

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Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy

Major Depressive Disorder, Irritability

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial