Clinical trial NCT01942785: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Major Depressive Disorder
Irritability
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2013-09-16
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Change From Baseline to Week 6 in SIS Total Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in SIS Item 1 Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in IDS-C30 Item 6 Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in Delay Discounting - Log-transformed MCQ Scores
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in BIS-11 Total Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in KSQ Anger-hostility Subscore
timeFrame: Baseline and Week 6
measure: Shift From Baseline to Week 6 in Anger Attacks (AAQ)
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in IDS-C30 Total Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in KSQ Depression Subscore
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in MADRS Total Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in CPFQ Total Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in CGI-S Score
timeFrame: Baseline and Week 6
measure: CGI-I Score at Week 6
timeFrame: Week 6
measure: Change From Baseline to Week 6 in KSQ Total Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in Delay Discounting - Log-transformed EDT DPDT Scores
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in Delay Discounting - EDT DRT Score
timeFrame: Baseline and Week 6
measure: Change From Week 6 to Week 10 in SIS Total Score
timeFrame: Week 6 and Week 10
measure: Change From Week 6 to Week 10 in SIS Item 1 Score
timeFrame: Week 6 and Week 10
measure: Change From Week 6 to Week 10 in Delay Discounting - MCQ Scores
timeFrame: Week 6 and Week 10
measure: Change From Week 6 to Week 10 in BIS-11 Total Score
timeFrame: Week 6 and Week 10
measure: Change From Week 6 to Week 10 in KSQ Anger-hostility Subscore
timeFrame: Week 6 and Week 10
measure: Change From Week 6 to Week 10 in KSQ Depression Subscore
timeFrame: Week 6 and Week 10
measure: Change From Week 6 to Week 10 in CGI-S Score
timeFrame: Week 6 and Week 10
measure: Change From Baseline to Week 6 in MADRS Total Score in Patients With a Pre-defined Baseline BIS-11 Total Score
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in CGI-S Score in Patients With a Pre-defined Baseline BIS-11 Total Score
timeFrame: Baseline and Week 6
measure: CGI-I Score at Week 6 Patients With a Pre-defined Baseline BIS-11 Total Score
timeFrame: Week 6
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: US015
state: Arizona
city: Glendale
country: United States
facility: US019
state: California
city: Oakland
country: United States
facility: US016
state: California
city: San Diego
country: United States
facility: US014
state: California
city: Denver
country: United States
facility: US011
state: Colorado
city: Hallandale Beach
country: United States
facility: US018
state: Florida
city: Jacksonville
country: United States
facility: US009
state: Florida
city: Orlando
country: United States
facility: US005
state: Florida
city: Gaithersburg
country: United States
facility: US006
state: Maryland
city: Weymouth
country: United States
facility: US012
state: Massachusetts
city: Jamaica
country: United States
facility: US003
state: New York
city: Dayton
country: United States
facility: US001
state: Ohio
city: Portland
country: United States
facility: US007
state: Oregon
city: Memphis
country: United States
facility: US004
state: Tennessee
city: Seattle
country: United States
facility: US002
state: Washington
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
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.