To Assess the Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD)

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01123707
• Collaborator: (none)
• Enrollment: 173
• Arms: 4
• Actual Duration (Months): 10.3

Study Details

Study Description

Brief Summary

This is a multicenter, 52-week, open-label study designed to assess the safety and tolerability of an oral aripiprazole/escitalopram combination therapy in outpatients with major depressive disorder (MDD). Enrollment into the study will be from eligible participants who have completed participation in Protocol 31-08-255 [NCT01111539], 31-08-256 [NCT01111552], or 31-08-263 [NCT01111565] ("rollover" participants).

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder (MDD)	Drug: Aripiprazole; Drug: Escitalopram	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 173 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Group composed of eligible rollover participants who completed one of the previous studies: 31-08-255 [NCT01111539], 31-08-256 [NCT01111552], or 31-08-263 [NCT01111565]Group composed of eligible rollover participants who completed one of the previous studies: 31-08-255 [NCT01111539], 31-08-256 [NCT01111552], or 31-08-263 [NCT01111565]
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, 52-week, Open-label Study to Assess the Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Patients With Major Depressive Disorder
• Actual Study Start Date: Nov 18, 2010
• Actual Primary Completion Date: Sep 27, 2011
• Actual Study Completion Date: Sep 27, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Prior Aripiprazole/Escitalopram Combination Therapy Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the maximum tolerated dose (MTD) by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Drug: Aripiprazole; Aripiprazole oral capsules; Other Names: OPC-14597 ; Drug: Escitalopram; Escitalopram oral capsules
Experimental: Prior Escitalopram Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Drug: Aripiprazole; Aripiprazole oral capsules; Other Names: OPC-14597 ; Drug: Escitalopram; Escitalopram oral capsules
Experimental: Prior Aripiprazole Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Drug: Aripiprazole; Aripiprazole oral capsules; Other Names: OPC-14597 ; Drug: Escitalopram; Escitalopram oral capsules
Experimental: Prior Single-blind Escitalopram Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.	Drug: Aripiprazole; Aripiprazole oral capsules; Other Names: OPC-14597 ; Drug: Escitalopram; Escitalopram oral capsules

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs), Severe (Grade 3 or Higher) TEAEs, and Discontinuations From the Trial Due to TEAEs [From first dose up to 30 days post last dose (Up to approximately 40 weeks)]

   An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-patient hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention. TEAE is defined as an adverse event that started after start of study drug treatment. The Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was used to determine the severity wherein Grade 1=mild AE, Grade 2=moderate AE, Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death related to AE.

Secondary Outcome Measures

1. Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score [Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)]

   The severity of illness was rated using a 7-point CGI-S. CGI-S scores range from 1 to 7, where 1=normal, not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill participants. A negative mean change from Baseline indicates improvement.

2. Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score [Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)]

   The severity of illness was rated using a 7-point PGI-S. PGI-S scores range from 1 to 7, where 1=not depressed at all, 2=only occasionally depressed to a mild degree, 3=mildly depressed half the time, 4=moderately depressed most of the time, 5=moderately depressed almost all of the time, 6=severely depressed all the time, 7=extremely depressed all the time. A negative mean change from Baseline indicates improvement.

3. Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities [Up to 40 weeks]

   Criteria for potentially clinically significant vital sign abnormalities: Heart rate [beats per minute (BPM)]: >120, increase >=15, <50, decrease >=15; systolic blood pressure [millimeter of mercury (mmHg)]: >180, increase >=20, <90, decrease >=20; diastolic blood pressure (mmHg): >105, increase >=15, <50, decrease >=15; orthostatic hypotension: >=20 mmHg decrease in systolic blood pressure and >=25 bpm increase in heart rate from supine to sitting; weight (kg) gain: increase >=7%; or weight loss: decrease >=7%. Only categories with at least 1 participant with event are reported.

4. Mean Change From Baseline in Body Weight [Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)]

5. Mean Change From Baseline in Body Mass Index (BMI) [Baseline, Week 26 and End of the study visit (Week 43 or before)]

   BMI= weight(kg)/[height(m)^2].

6. Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities [Up to 40 weeks]

   The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant lab values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance. The categories with at least one participants with abnormal lab value as assessed by the Investigator are reported.

7. Mean Change From Baseline in Laboratory Test Results: Prolactin [Baseline, Weeks 8, 26, and End of the study visit (Week 43 or before)]

   Prolactin is a hormone released by the pituitary gland. The prolactin test measures the amount of prolactin in the blood. Prolactin is responsible for the breast growth and milk production during pregnancy and after birth. The normal prolactin levels range from 20 to 25 ng/mL in males and females and 80 to 400 ng/mL in pregnant women. A negative mean change from Baseline indicates reduction in the prolactin levels.

8. Mean Change From Baseline in Laboratory Test Results: Hemoglobin A1c (HbA1c) [Baseline, Week 8, and End of the study visit (Week 43 or before)]

   The HbA1c is also known as glycosylated hemoglobin. It is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound. The mean change in the value of HbA1c was analyzed relative to Baseline. The HbA1c of <6.0% signifies the normal blood glucose level. A negative mean change from Baseline indicates improvement.

9. Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities [Up to 40 weeks]

   Incidence of clinically relevant abnormal ECG values were reported as change from Baseline in heart rate (Tachycardia - ≥15 beats per minute (bpm), Bradycardia ≤15 bpm; Rhythm (Sinus tachycardia ≥15 bpm increase, Sinus bradycardia decrease of ≥15 bpm from Baseline); Presence of - supraventricular premature beat; ventricular premature beat; supraventricular tachycardia; ventricular tachycardia; atrial fibrillation and flutter. Conduction - Presence of primary, secondary or tertiary atrioventricular block, left bundle-branch block, right bundle-branch block, pre-excitation syndrome, other intraventricular conduction blocked QRS ≥0.12 second increase of ≥0.02 second. Acute, subacute or old Infarction, Presence of myocardial ischemia, symmetrical T-wave inversion. Increase in QTc - QTc ≥450 msec ≥10% increase. Any clinically significant change from Baseline assessed by the Investigator are reported. Only categories with at least 1 participant with event are reported.

10. Number of Participants With Potentially Clinically Significant Physical Examination Findings [Up to 40 weeks]

11. Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score [Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)]

    The AIMS is a 12-item scale. The first 10 -items are rated from 0 to 4 (0=best, 4=worst). An item score of 0, depending on the item, either means: no abnormal involuntary movement (AIM), or no incapacitation due to AIM, or no awareness of AIM. An item score of 4 either means: severe AIM, or severe incapacitation due to AIM, or being aware of, and severe distress caused by AIM. Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28, where a higher score indicates worst outcome. A negative mean change from Baseline indicates improvement.

12. Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score [Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)]

    The SAS is a rating scale used to measure extrapyramidal symptoms (EPS). The SAS is a 10-item scale, with each item rated from 1 to 5, with 1 being normal and 5 being the worst. The SAS total score is the sum of ratings for all 10 items, with possible total scores from 10 to 50. A negative mean change from Baseline indicates improvement.

13. Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score [Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)]

    The BARS is used to assess the presence and severity of akathisia. This scale consists of 4 items. Only item 4, the 'Global Clinical Assessment of Akathisia', was evaluated for this outcome measure. This item is rated on a 6-point scale, with 0 being best (absent) and 5 being worst (severe akathisia). A negative mean change from Baseline indicates improvement.

14. Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline; Weeks 1, 2, 4, 6, 8, 14 and Last Visit (Week 43 or before)]

    The suicidal ideation compared to Baseline was measured by an increase in suicidal ideation category (1-5 on the C-SSRS) during treatment from the maximum suicidal ideation category at Baseline, or any suicidal ideation during treatment if there is none at Baseline. C-SSRS is used to assess whether participant experienced suicidal ideation (Question 1: wish to be dead; Question 2: non-specific active suicidal thoughts; Question 3: active suicidal ideation with any methods (not plan) without intent to act; Question 4: active suicidal ideation with some intent to act, without specific plan; Question 5: active suicidal ideation with specific plan and intent). A negative change from Baseline indicates improvement. Only those categories and timepoints which have data are reported.

15. Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score [Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)]

    The MGH SFI is a measure of a participant's self-reported sexual functioning. The MGH SFI included 5 questions at the baseline assessment, each addressing experiences over the last month: Question a) interest in sex, Question b) ability to get sexually aroused, Question c) ability to achieve orgasm, Question d) ability to get and maintain an erection, and Question e) overall sexual satisfaction. The MGH SFI at post-baseline visits included one additional question: Question f) overall improvement since the last medication change. Each question/item is rated from 1 through 6. For questions a) through e), a score of 1 indicates 'greater than normal', and 6 'totally absent'. For question f), a score of 1 indicates 'very much improved', and 6 'much worse'. All question scores are analyzed separately. No total or mean score is derived. Each subscale score ranges from 0 to 6, higher scores indicates worsening. A negative mean change from Baseline indicates improvement.

16. Mean Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) Overall General Subscore [Baseline, Week 8, 26 and End of the study visit (Week 43 or before)]

    The Q-LES-Q-SF is a self-report measure designed to enable investigators to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning with the help of 14 items of total 16 items of the scale. The overall general subscore is obtained using 14 items of the scale. Each item is scored on a 5-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. The raw scores are computed to an overall general subscore of 0 to 100 where lower scores indicate less enjoyment or satisfaction with the activity. A positive change from Baseline indicates improvement.

17. Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Total Score [Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)]

    The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all, to 10= extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The SDS Mean Score of 0 to 10 was calculated as an average of the three item scores. All three item scores needed to be available with the exception of the work/school item score when this item was not applicable. A negative mean change from Baseline indicates improvement.

18. Mean Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score [Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)]

    The CPFQ is a brief self-rated scale developed to measure cognitive and executive dysfunction in mood and anxiety disorders. It consists of 7 items. The CPFQ total score ranges from 7 to 42, with higher score representing less satisfaction in cognitive and physical functioning. A negative mean change from Baseline indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 66 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants who participated in Protocol 31-08-255, 31-08-256, or 31-08-263.

Exclusion Criteria:

• Participants with a current need for involuntary commitment or who have been hospitalized ≤ 28 days of the Baseline Visit for the current major depressive episode.

• Participants with a diagnosis of delirium, dementia, amnestic or other cognitive disorder, schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder, eating disorder (including anorexia nervosa or bulimia), obsessive compulsive disorder, panic disorder, or posttraumatic stress disorder.

• Participants with a diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.

• Participants experiencing hallucinations, delusions, or any psychotic symptomatology in the current depressive episode.

• Participants who have met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for substance abuse in the past 6 months (prior to the Baseline Visit) and/or dependence up to and including the past 12 months (prior to the Baseline Visit), including alcohol and benzodiazepines, but excluding caffeine and nicotine. Participants with two positive drug results for cocaine should be excluded from the study.

• Participants with hypothyroidism or hyperthyroidism.

• Participants with a significant risk of committing suicide based on history, investigator's judgment, and/or evaluation based on the Columbia-Suicide Severity Rating Scale (C-SSRS).

• Participants who currently have clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders.

• Participants with insulin-dependent diabetes mellitus (IDDM).

• Participants with epilepsy or significant history of seizure disorders, except for a single childhood febrile seizure, post-traumatic, etc.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT01123707
• Other Study ID Numbers: 31-08-257; 2010-018860-17
• First Posted: May 14, 2010
• Last Update Posted: Dec 22, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.: Major Depressive Disorder; MDD; Depression
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Aripiprazole; Citalopram

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 67 investigative sites in Australia, Estonia, India, Mexico, South Korea, and the United States from 18 November 2010 to 27 September 2011.
Pre-assignment Detail	A total of 173 participants from studies 31-08-255 (NCT01111539), 31-08-256 (NCT01111552), and 31-08-263 (NCT01111565) were enrolled, of which 170 participants received aripiprazole/escitalopram combination therapy and were analyzed in this 31-08-257 study (NCT01123707). The data is reported as per the treatment received in previous studies.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the maximum tolerated dose (MTD) by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Period Title: Overall Study
STARTED	44	41	38	50
Safety Sample	44	41	36	49
COMPLETED	0	0	0	0
NOT COMPLETED	44	41	38	50

Baseline Characteristics

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram	Total
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.	Total of all reporting groups
Overall Participants	44	41	36	49	170
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.1 (12.0)	45.8 (10.7)	48.6 (10.8)	43.4 (11.3)	45.8 (11.3)
Sex: Female, Male (Count of Participants)
Female	34 77.3%	25 61%	26 72.2%	33 67.3%	118 69.4%
Male	10 22.7%	16 39%	10 27.8%	16 32.7%	52 30.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 18.2%	7 17.1%	4 11.1%	5 10.2%	24 14.1%
Not Hispanic or Latino	36 81.8%	34 82.9%	32 88.9%	43 87.8%	145 85.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	1 2%	1 0.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 4.5%	1 2.4%	1 2.8%	1 2%	5 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 15.9%	7 17.1%	5 13.9%	5 10.2%	24 14.1%
White	33 75%	31 75.6%	30 83.3%	42 85.7%	136 80%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 4.5%	2 4.9%	0 0%	1 2%	5 2.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs), Severe (Grade 3 or Higher) TEAEs, and Discontinuations From the Trial Due to TEAEs
Description	An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it did not necessarily have to have a causal relationship with this treatment. An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-patient hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention. TEAE is defined as an adverse event that started after start of study drug treatment. The Common Terminology Criteria for Adverse Events v3.0 (CTCAE) was used to determine the severity wherein Grade 1=mild AE, Grade 2=moderate AE, Grade 3=severe AE, Grade 4=life-threatening or disabling AE, Grade 5=death related to AE.
Time Frame	From first dose up to 30 days post last dose (Up to approximately 40 weeks)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
TEAEs	54.5 123.9%	70.7 172.4%	75.0 208.3%	67.3 137.3%
STEAEs	2.3 5.2%	9.8 23.9%	0.0 0%	0.0 0%
Severe (Grade 3 or Higher) TEAEs	0.0 0%	4.9 12%	5.6 15.6%	2.0 4.1%
Discontinuations from the Trial due to TEAEs	11.4 25.9%	17.1 41.7%	13.9 38.6%	6.1 12.4%

2. Secondary Outcome

Title	Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score
Description	The severity of illness was rated using a 7-point CGI-S. CGI-S scores range from 1 to 7, where 1=normal, not at all ill, 2=borderline mentally ill, 3=mildly ill, 4=moderately ill, 5=markedly ill, 6=severely ill, 7=among the most extremely ill participants. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Sample included all participants in the Safety Sample with at least one CGI-S assessment in the Treatment Phase, with data available for analysis. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	48
Baseline	3.1 (1.1)	3.4 (1.2)	3.4 (0.9)	3.2 (0.7)
Change from Baseline at Week 1	-0.0 (0.7)	-0.2 (0.6)	-0.2 (0.6)	-0.4 (0.9)
Change from Baseline at Week 2	-0.3 (0.8)	-0.3 (0.7)	-0.4 (0.6)	-0.9 (0.9)
Change from Baseline at Week 4	-0.1 (0.9)	-0.5 (0.8)	-0.6 (1.0)	-0.9 (0.9)
Change from Baseline at Week 6	-0.3 (0.8)	-0.5 (0.9)	-0.5 (1.1)	-0.9 (0.6)
Change from Baseline at Week 8	-0.3 (0.8)	-0.5 (0.7)	-0.7 (0.9)	-0.7 (1.0)
Change from Baseline at Week 14	-0.3 (1.4)	-0.6 (0.7)	-1.0 (1.2)	-0.7 (1.0)
Change from Baseline at Week 20	-0.6 (0.7)	-0.3 (1.0)	-1.2 (1.1)	-0.9 (0.7)
Change from Baseline at Week 26	-0.8 (0.4)	0.0 (0.0)	-1.0 (1.4)	-1.3 (0.8)
Change from Baseline at Week 32	-1.0 (NA)	-2.0 (NA)	-2.0 (1.0)
Change from Baseline at End of the Study Visit (Week 43 or before)	-0.2 (1.1)	-0.6 (0.9)	-0.7 (1.1)	-0.9 (1.0)

3. Secondary Outcome

Title	Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score
Description	The severity of illness was rated using a 7-point PGI-S. PGI-S scores range from 1 to 7, where 1=not depressed at all, 2=only occasionally depressed to a mild degree, 3=mildly depressed half the time, 4=moderately depressed most of the time, 5=moderately depressed almost all of the time, 6=severely depressed all the time, 7=extremely depressed all the time. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Sample included all participants in the Safety Sample with at least one CGI-S assessment in the Treatment Phase, with data available for analysis. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	48
Baseline	2.8 (1.2)	3.1 (1.2)	3.3 (1.2)	3.2 (1.4)
Change from Baseline at Week 1	0.1 (0.8)	-0.2 (0.7)	-0.2 (0.8)	-0.6 (1.0)
Change from Baseline at Week 2	-0.2 (0.9)	-0.4 (0.9)	-0.4 (0.7)	-1.0 (1.2)
Change from Baseline at Week 4	0.0 (1.1)	-0.5 (1.0)	-0.2 (1.0)	-0.9 (1.5)
Change from Baseline at Week 6	-0.1 (0.9)	-0.4 (1.3)	-0.4 (0.9)	-1.1 (1.1)
Change from Baseline at Week 8	-0.2 (1.0)	-0.4 (1.0)	-0.3 (0.9)	-0.9 (1.5)
Change from Baseline at Week 14	-0.1 (1.8)	-0.2 (1.2)	-0.8 (1.2)	-0.9 (1.4)
Change from Baseline at Week 20	-0.4 (0.9)	-0.3 (1.2)	-1.0 (1.1)	-1.3 (1.3)
Change from Baseline at Week 26	0.0 (1.4)	0.0 (0.0)	-0.6 (2.1)	-1.0 (1.1)
Change from Baseline at Week 32	0.0 (NA)	-1.0 (NA)	0.0 (1.0)
Change from Baseline at End of Study Visit (Week 43 or before)	-0.1 (1.2)	-0.3 (1.2)	-0.3 (1.2)	-0.9 (1.5)

4. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities
Description	Criteria for potentially clinically significant vital sign abnormalities: Heart rate [beats per minute (BPM)]: >120, increase >=15, <50, decrease >=15; systolic blood pressure [millimeter of mercury (mmHg)]: >180, increase >=20, <90, decrease >=20; diastolic blood pressure (mmHg): >105, increase >=15, <50, decrease >=15; orthostatic hypotension: >=20 mmHg decrease in systolic blood pressure and >=25 bpm increase in heart rate from supine to sitting; weight (kg) gain: increase >=7%; or weight loss: decrease >=7%. Only categories with at least 1 participant with event are reported.
Time Frame	Up to 40 weeks

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the number of participants with at least one post-baseline numeric result for the given vital sign parameter.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Orthostatic Hypotension (mmHg)	0 0%	0 0%	1 2.8%	0 0%
Weight (kg): Weight Gain >=7%	4 9.1%	0 0%	2 5.6%	4 8.2%
Weight (kg): Weight Loss >=7%	5 11.4%	2 4.9%	1 2.8%	2 4.1%

5. Secondary Outcome

Title	Mean Change From Baseline in Body Weight
Time Frame	Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the number of participants with data available for analysis at the given timepoint.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Baseline	93.0 (27.1)	88.3 (23.5)	87.0 (24.2)	84.7 (22.6)
Change from Baseline at Week 1	0.0 (2.4)	0.1 (1.8)	0.1 (1.2)	0.1 (1.3)
Change from Baseline at Week 2	0.5 (2.6)	0.2 (2.1)	0.2 (1.4)	0.4 (1.5)
Change from Baseline at Week 4	0.3 (3.8)	0.4 (2.3)	0.4 (1.4)	0.2 (2.1)
Change from Baseline at Week 6	0.3 (4.5)	0.1 (2.9)	0.3 (2.1)	0.3 (2.8)
Change from Baseline at Week 8	-0.0 (5.5)	-0.5 (3.2)	0.4 (2.7)	0.2 (2.7)
Change from Baseline at Week 14	2.0 (5.1)	-0.9 (4.8)	0.7 (3.0)	0.6 (4.3)
Change from Baseline at Week 20	3.8 (2.6)	2.0 (1.6)	0.4 (5.7)	1.4 (1.4)
Change from Baseline at Week 26	5.7 (NA)	1.4 (NA)	3.3 (0.5)
Change from Baseline at Week 32	-3.6 (NA)
Change from Baseline at Last Visit (Week 43 or before)	-0.2 (4.7)	0.1 (3.1)	0.1 (4.0)	1.0 (3.7)

6. Secondary Outcome

Title	Mean Change From Baseline in Body Mass Index (BMI)
Description	BMI= weight(kg)/[height(m)^2].
Time Frame	Baseline, Week 26 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the number of participants with at least one observation at the given timepoint.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Baseline	33.4 (8.6)	30.9 (8.1)	31.1 (7.6)	30.7 (7.4)
Change from Baseline at Week 26	2.3 (NA)	0.4 (NA)	1.2 (0.2)
Change from Baseline at Last Visit (Week 43 or before)	0.0 (2.5)	-0.1 (1.1)	-0.1 (1.5)	0.4 (1.7)

7. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities
Description	The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant lab values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance. The categories with at least one participants with abnormal lab value as assessed by the Investigator are reported.
Time Frame	Up to 40 weeks

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the total number of participants with at least one post-baseline numeric result for the given lab test.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Alanine Aminotransferase [Serum Glutamic Pyruvic Transaminase (SGPT)] [unit(U)/L]: >=3×ULN	0 0%	1 2.4%	0 0%	0 0%
Aspartate Aminotransferase [Serum Glutamic Oxaloacetic Transaminase (SGOT)] (U/L): >=3×ULN	0 0%	1 2.4%	0 0%	0 0%
Bilirubin, Total [mg/deciliter(dL)]: ≥2.0	0 0%	1 2.4%	0 0%	0 0%
Cholesterol, Total, Fasting (mg/dL): ≥240	10 22.7%	9 22%	5 13.9%	8 16.3%
Creatine phosphokinase (CPK), Total (U/L): ≥3 x ULN	0 0%	1 2.4%	0 0%	1 2%
High-density Lipoprotein (HDL) Cholesterol, Fasting (mg/dL): ≤30	0 0%	0 0%	2 5.6%	1 2%
Low-density Lipoprotein (LDL) Cholesterol, Fasting (mg/dL): ≥160	6 13.6%	5 12.2%	4 11.1%	8 16.3%
Triglycerides, Fasting (mg/dL): Men ≥160; Women ≥120	24 54.5%	16 39%	14 38.9%	25 51%
Urea Nitrogen (mg/dL); >= 30 mg/dL	0 0%	0 0%	1 2.8%	0 0%
Uric Acid (mg/dL): Men ≥10.5; Women ≥8.5	0 0%	0 0%	0 0%	1 2%
Eosinophils (%): ≥10	0 0%	1 2.4%	0 0%	0 0%
Hematocrit (%): Female ≤32%; Male: ≤37% or 3 point decrease from baseline	0 0%	1 2.4%	1 2.8%	0 0%
Hemoglobin (g/dL): Men ≤11.5; Women ≤9.5	1 2.3%	0 0%	1 2.8%	0 0%
Prolactin [nanograms (ng)/mL]: >1 ULN	1 2.3%	1 2.4%	1 2.8%	0 0%

8. Secondary Outcome

Title	Mean Change From Baseline in Laboratory Test Results: Prolactin
Description	Prolactin is a hormone released by the pituitary gland. The prolactin test measures the amount of prolactin in the blood. Prolactin is responsible for the breast growth and milk production during pregnancy and after birth. The normal prolactin levels range from 20 to 25 ng/mL in males and females and 80 to 400 ng/mL in pregnant women. A negative mean change from Baseline indicates reduction in the prolactin levels.
Time Frame	Baseline, Weeks 8, 26, and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the total number of participants with at least one observation of the given parameter.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Mean Change from Baseline at Week 8	0.52 (3.94)	0.31 (4.37)	0.62 (3.26)	-1.10 (6.88)
Mean Change from Baseline at Week 26	-0.79 (NA)	-2.75 (NA)	-0.75 (0.52)
Mean Change from Baseline at Week Last Visit (Week 43 or before)	0.37 (4.37)	1.33 (4.71)	0.30 (3.25)	-0.49 (5.57)

9. Secondary Outcome

Title	Mean Change From Baseline in Laboratory Test Results: Hemoglobin A1c (HbA1c)
Description	The HbA1c is also known as glycosylated hemoglobin. It is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound. The mean change in the value of HbA1c was analyzed relative to Baseline. The HbA1c of <6.0% signifies the normal blood glucose level. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline, Week 8, and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the total number of participants with at least one observation of the given parameter.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	1	1	0	0
Mean Change from Baseline at Week 8	0.30 (NA)
Mean Change from Baseline at Last Visit (Week 43 or before)	-0.30 (NA)	0.30 (NA)

10. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
Description	Incidence of clinically relevant abnormal ECG values were reported as change from Baseline in heart rate (Tachycardia - ≥15 beats per minute (bpm), Bradycardia ≤15 bpm; Rhythm (Sinus tachycardia ≥15 bpm increase, Sinus bradycardia decrease of ≥15 bpm from Baseline); Presence of - supraventricular premature beat; ventricular premature beat; supraventricular tachycardia; ventricular tachycardia; atrial fibrillation and flutter. Conduction - Presence of primary, secondary or tertiary atrioventricular block, left bundle-branch block, right bundle-branch block, pre-excitation syndrome, other intraventricular conduction blocked QRS ≥0.12 second increase of ≥0.02 second. Acute, subacute or old Infarction, Presence of myocardial ischemia, symmetrical T-wave inversion. Increase in QTc - QTc ≥450 msec ≥10% increase. Any clinically significant change from Baseline assessed by the Investigator are reported. Only categories with at least 1 participant with event are reported.
Time Frame	Up to 40 weeks

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the total number of participants with baseline and at least one post-baseline numeric result for the given ECG parameter.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Bradycardia: Decrease of ≥15 bpm	1 2.3%	0 0%	0 0%	0 0%
Sinus Bradycardia: Decrease of ≥15 bpm	1 2.3%	0 0%	0 0%	0 0%
Supraventricular Premature Beat: Not Present to Present	1 2.3%	0 0%	1 2.8%	0 0%
Ventricular Premature Beat: Not Present to Present	0 0%	1 2.4%	1 2.8%	0 0%
1° Atrioventricular Block: Increase of ≥0.05 second	0 0%	1 2.4%	0 0%	0 0%
Right Bundle-branch Block: Not Present to Present	1 2.3%	0 0%	0 0%	1 2%
Myocardial Ischemia: Not Present to Present	1 2.3%	0 0%	0 0%	0 0%
Symmetrical T-wave Inversion: Not Present to Present	3 6.8%	1 2.4%	0 0%	0 0%
QTcB	1 2.3%	1 2.4%	2 5.6%	0 0%
QTcF	0 0%	1 2.4%	2 5.6%	1 2%
QTcN	0 0%	1 2.4%	1 2.8%	0 0%

11. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Physical Examination Findings
Time Frame	Up to 40 weeks

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
Description	The AIMS is a 12-item scale. The first 10 -items are rated from 0 to 4 (0=best, 4=worst). An item score of 0, depending on the item, either means: no abnormal involuntary movement (AIM), or no incapacitation due to AIM, or no awareness of AIM. An item score of 4 either means: severe AIM, or severe incapacitation due to AIM, or being aware of, and severe distress caused by AIM. Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28, where a higher score indicates worst outcome. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Baseline	0.1 (0.5)	0.0 (0.2)	0.1 (0.3)	0.1 (0.3)
Change from Baseline at Week 4	-0.1 (0.5)	-0.0 (0.2)	0.0 (0.2)	0.2 (1.1)
Change from Baseline at Week 8	-0.1 (0.6)	0.0 (0.0)	0.0 (0.0)	-0.1 (0.4)
Change from Baseline at Week 20	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)	-0.2 (0.6)
Change from Baseline at Week 26	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)
Change from Baseline at Week 32	0.0 (NA)	0.0 (NA)	0.0 (0.0)
Change from Baseline at End of Study Visit (Week 43 or before)	-0.0 (0.5)	-0.0 (0.2)	-0.0 (0.4)	-0.0 (0.3)

13. Secondary Outcome

Title	Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score
Description	The SAS is a rating scale used to measure extrapyramidal symptoms (EPS). The SAS is a 10-item scale, with each item rated from 1 to 5, with 1 being normal and 5 being the worst. The SAS total score is the sum of ratings for all 10 items, with possible total scores from 10 to 50. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Baseline	10.1 (0.3)	10.0 (0.2)	10.3 (0.7)	10.1 (0.5)
Change from Baseline at Week 4	0.0 (0.3)	0.3 (0.7)	0.0 (0.7)	0.1 (0.5)
Change from Baseline at Week 8	-0.1 (0.4)	0.2 (0.5)	-0.1 (0.7)	-0.0 (1.0)
Change from Baseline at Week 20	0.0 (0.0)	0.0 (0.0)	-0.3 (0.7)	-0.3 (0.6)
Change from Baseline at Week 26	0.0 (0.0)	0.0 (0.0)	0.0 (0.0)	-0.3 (0.8)
Change from Baseline at Week 32	0.0 (NA)	0.0 (NA)	-0.7 (1.2)
Change from Baseline at End of Study Visit (Week 43 or before)	0.1 (1.1)	0.3 (0.8)	0.1 (1.1)	-0.0 (0.5)

14. Secondary Outcome

Title	Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score
Description	The BARS is used to assess the presence and severity of akathisia. This scale consists of 4 items. Only item 4, the 'Global Clinical Assessment of Akathisia', was evaluated for this outcome measure. This item is rated on a 6-point scale, with 0 being best (absent) and 5 being worst (severe akathisia). A negative mean change from Baseline indicates improvement.
Time Frame	Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Baseline	0.2 (0.5)	0.1 (0.4)	0.4 (0.8)	0.1 (0.4)
Change from Baseline at Week 4	0.1 (0.6)	0.3 (0.7)	0.0 (0.8)	0.2 (0.6)
Change from Baseline at Week 8	-0.1 (0.6)	0.3 (1.0)	-0.1 (1.1)	-0.0 (0.6)
Change from Baseline at Week 20	-0.1 (0.4)	-0.2 (0.4)	-0.4 (1.0)	-0.3 (0.9)
Change from Baseline at Week 26	-0.2 (0.4)	-0.5 (0.7)	0.0 (0.0)	0.0 (0.0)
Change from Baseline at Week 32	0.0 (NA)	-1.0 (NA)	-0.3 (0.6)
Change from Baseline at End of Study Visit (Week 43 or before)	-0.0 (0.6)	0.3 (0.9)	-0.1 (1.1)	0.0 (0.5)

15. Secondary Outcome

Title	Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description	The suicidal ideation compared to Baseline was measured by an increase in suicidal ideation category (1-5 on the C-SSRS) during treatment from the maximum suicidal ideation category at Baseline, or any suicidal ideation during treatment if there is none at Baseline. C-SSRS is used to assess whether participant experienced suicidal ideation (Question 1: wish to be dead; Question 2: non-specific active suicidal thoughts; Question 3: active suicidal ideation with any methods (not plan) without intent to act; Question 4: active suicidal ideation with some intent to act, without specific plan; Question 5: active suicidal ideation with specific plan and intent). A negative change from Baseline indicates improvement. Only those categories and timepoints which have data are reported.
Time Frame	Baseline; Weeks 1, 2, 4, 6, 8, 14 and Last Visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Question 1: Baseline	0.0 0%	12.2 29.8%	8.3 23.1%	4.1 8.4%
Question 1: Week 1	0.0 0%	2.4 5.9%	2.8 7.8%	0.0 0%
Question 1: Week 2	0.0 0%	2.4 5.9%	2.8 7.8%	0.0 0%
Question 1: Week 4	2.3 5.2%	4.9 12%	2.8 7.8%	0.0 0%
Question 1: Week 6	2.3 5.2%	4.9 12%	2.8 7.8%	0.0 0%
Question 1: Week 8	0.0 0%	0.0 0%	2.8 7.8%	2.0 4.1%
Question 1: Week 14	2.3 5.2%	0.0 0%	0.0 0%	0.0 0%
Question 1: Last Visit (Week 43 or before)	2.3 5.2%	2.4 5.9%	5.6 15.6%	0.0 0%
Question 2: Week 8	0.0 0%	0.0 0%	0.0 0%	2.0 4.1%
Question 2: Week 14	2.3 5.2%	0.0 0%	0.0 0%	0.0 0%
Question 2: Last Visit (Week 43 or before)	0.0 0%	0.0 0%	2.8 7.8%	0.0 0%
Question 3: Week 14	2.3 5.2%	0.0 0%	0.0 0%	0.0 0%
Question 3: Last Visit (Week 43 or before)	0.0 0%	0.0 0%	2.8 7.8%	0.0 0%

16. Secondary Outcome

Title	Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score
Description	The MGH SFI is a measure of a participant's self-reported sexual functioning. The MGH SFI included 5 questions at the baseline assessment, each addressing experiences over the last month: Question a) interest in sex, Question b) ability to get sexually aroused, Question c) ability to achieve orgasm, Question d) ability to get and maintain an erection, and Question e) overall sexual satisfaction. The MGH SFI at post-baseline visits included one additional question: Question f) overall improvement since the last medication change. Each question/item is rated from 1 through 6. For questions a) through e), a score of 1 indicates 'greater than normal', and 6 'totally absent'. For question f), a score of 1 indicates 'very much improved', and 6 'much worse'. All question scores are analyzed separately. No total or mean score is derived. Each subscale score ranges from 0 to 6, higher scores indicates worsening. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	44	41	36	49
Question a: Baseline	4.2 (1.7)	3.8 (1.5)	4.4 (1.4)	3.6 (1.6)
Question a: Change from Baseline at Week 8	-0.1 (1.3)	-0.4 (0.9)	-0.4 (0.8)	-0.3 (1.1)
Question a: Change from Baseline at Week 26	-0.2 (0.4)	0.0 (0.0)	-0.4 (1.1)	0.0 (0.0)
Question a: Change from Baseline at End of Study Visit (Week 43 or before)	-0.1 (1.1)	-0.3 (1.1)	-0.4 (1.2)	-0.4 (1.2)
Question b: Baseline	3.9 (1.7)	3.7 (1.5)	4.1 (1.4)	3.5 (1.6)
Question b: Change from Baseline at Week 8	0.0 (0.9)	-0.2 (0.9)	-0.1 (0.9)	-0.3 (0.9)
Question b: Change from Baseline at Week 26	0.2 (0.4)	0.0 (0.0)	0.0 (1.2)	-0.2 (0.4)
Question b: Change from Baseline at End of Study Visit (Week 43 or before)	0.1 (0.8)	-0.3 (1.0)	-0.2 (1.0)	-0.3 (1.1)
Question c: Baseline	4.0 (1.7)	3.8 (1.5)	4.1 (1.5)	3.5 (1.6)
Question c: Change from Baseline at Week 8	-0.1 (1.0)	-0.3 (1.1)	-0.1 (0.9)	-0.2 (0.9)
Question c: Change from Baseline at Week 26	-0.2 (1.1)	0.0 (0.0)	-0.2 (1.3)	-0.2 (0.4)
Question c: Change from Baseline at End of Study Visit (Week 43 or before)	-0.0 (1.0)	-0.4 (1.1)	0.0 (1.1)	-0.1 (1.1)
Question d: Baseline	2.5 (1.2)	3.0 (1.4)	3.6 (1.3)	2.9 (1.3)
Question d: Change from Baseline at Week 8	0.0 (0.0)	0.0 (0.5)	-0.4 (0.5)	-0.2 (0.4)
Question d: Change from Baseline at Week 26	0.0 (NA)	0.5 (0.7)	0.0 (NA)	0.0 (0.0)
Question d: Change from Baseline at End of Study Visit (Week 43 or before)	0.1 (0.3)	0.0 (0.5)	0.1 (0.9)	-0.1 (0.8)
Question e: Baseline	4.2 (1.7)	3.9 (1.6)	4.4 (1.3)	3.7 (1.6)
Question e: Change from Baseline at Week 8	-0.1 (1.1)	-0.3 (0.8)	-0.3 (0.8)	-0.2 (1.1)
Question e: Change from Baseline at Week 26	-0.4 (0.5)	0.5 (0.7)	-0.4 (1.1)	0.0 (0.6)
Question e: Change from Baseline at End of Study Visit (Week 43 or before)	-0.1 (0.9)	-0.3 (1.2)	-0.3 (1.4)	-0.3 (1.4)
Question f: Baseline	3.3 (0.9)	3.5 (1.2)	3.4 (1.1)	3.6 (1.2)
Question f: Change from Baseline at Week 8	0.1 (1.1)	-0.3 (1.1)	0.2 (1.1)	-0.7 (1.7)
Question f: Change from Baseline at Week 26	-1.0 (0.7)	0.0 (0.0)	0.4 (1.9)	-0.8 (1.3)
Question f: Change from Baseline at End of Study Visit (Week 43 or before)	-0.0 (1.0)	-0.2 (1.1)	-0.0 (1.6)	-0.6 (1.5)

17. Secondary Outcome

Title	Mean Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) Overall General Subscore
Description	The Q-LES-Q-SF is a self-report measure designed to enable investigators to easily obtain sensitive measures of the degree of enjoyment and satisfaction experienced by participants in various areas of daily functioning with the help of 14 items of total 16 items of the scale. The overall general subscore is obtained using 14 items of the scale. Each item is scored on a 5-point scale, with 1= Very Poor; 2=Poor; 3=Fair; 4=Good; 5=Very Good. The raw scores are computed to an overall general subscore of 0 to 100 where lower scores indicate less enjoyment or satisfaction with the activity. A positive change from Baseline indicates improvement.
Time Frame	Baseline, Week 8, 26 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record, with data available for analysis. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	43	41	36	49
Baseline	49.4 (14.7)	50.2 (19.9)	47.9 (16.8)	52.2 (14.6)
Change from Baseline at Week 8	0.8 (10.4)	3.6 (11.0)	6.2 (9.9)	9.5 (13.6)
Change from Baseline at Week 26	0.8 (19.6)	-0.5 (2.1)	6.2 (22.4)	4.3 (17.7)
Change from Baseline at End of Study visit (Week 43 or before)	1.0 (14.1)	5.0 (15.4)	4.6 (14.3)	10.0 (16.5)

18. Secondary Outcome

Title	Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Total Score
Description	The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0= not at all, to 10= extremely. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The SDS Mean Score of 0 to 10 was calculated as an average of the three item scores. All three item scores needed to be available with the exception of the work/school item score when this item was not applicable. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record, with data available for analysis. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	43	41	36	49
Baseline	4.6 (2.6)	4.3 (2.7)	5.1 (2.7)	3.8 (2.1)
Change from Baseline at Week 8	-1.1 (2.1)	-0.8 (1.6)	-2.0 (2.4)	-1.4 (1.8)
Change from Baseline at Week 26	-1.9 (1.6)	1.7 (2.4)	-2.6 (2.7)	-0.7 (4.6)
Change from Baseline at End of Study visit (Week 43 or before)	-0.6 (2.1)	-0.5 (2.5)	-1.6 (2.8)	-1.6 (2.2)

19. Secondary Outcome

Title	Mean Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score
Description	The CPFQ is a brief self-rated scale developed to measure cognitive and executive dysfunction in mood and anxiety disorders. It consists of 7 items. The CPFQ total score ranges from 7 to 42, with higher score representing less satisfaction in cognitive and physical functioning. A negative mean change from Baseline indicates improvement.
Time Frame	Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)

Outcome Measure Data

Analysis Population Description

Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record, with data available for analysis. Number analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy	Prior Escitalopram	Prior Aripiprazole	Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
Measure Participants	43	41	34	49
Baseline	23.0 (6.1)	22.1 (6.5)	24.4 (5.3)	22.0 (6.1)
Change from Baseline at Week 8	-1.3 (4.1)	-1.8 (2.6)	-2.2 (3.3)	-4.8 (7.7)
Change from Baseline at Week 26	-3.8 (3.5)	2.0 (0.0)	-2.2 (5.6)	-2.5 (6.0)
Change from Baseline at End of Study Visit (Week 43 or before)	-1.0 (4.6)	-0.2 (4.8)	-2.6 (5.0)	-3.5 (7.6)

Adverse Events

Time Frame	From first dose of study drug through 30 days post last dose (Up to 40 weeks)
Adverse Event Reporting Description	Safety Sample included all participants who received in the Treatment Phase at least one dose of aripiprazole/escitalopram combination medication as indicated on the dosing record.
Arm/Group Title	Prior Aripiprazole/Escitalopram Combination Therapy		Prior Escitalopram		Prior Aripiprazole		Prior Single-blind Escitalopram
Arm/Group Description	Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole/escitalopram combination therapy in the double-blind treatment period in previous studies were included in this group.		Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the double-blind treatment period in previous studies were included in this group.		Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received aripiprazole in the double-blind treatment period in previous studies were included in this group.		Aripiprazole capsules, orally at the daily dose of 3, 6, or 12 mg, in combination with escitalopram 10 or 20 mg orally, once daily in combination with escitalopram 10 or 20 mg (i.e., the final dose taken during the previous study), orally, once daily, for 36 weeks. Participants were titrated to the aripiprazole target dose of 12 mg/day at Week 1 if the initial 6 mg/day dose was tolerated. The dose adjustments were allowed for aripiprazole to establish the MTD by Week 4. Participants who received escitalopram in the single-blind treatment period in previous studies were included in this group.
All Cause Mortality
	Prior Aripiprazole/Escitalopram Combination Therapy		Prior Escitalopram		Prior Aripiprazole		Prior Single-blind Escitalopram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/41 (0%)		0/36 (0%)		0/49 (0%)
Serious Adverse Events
	Prior Aripiprazole/Escitalopram Combination Therapy		Prior Escitalopram		Prior Aripiprazole		Prior Single-blind Escitalopram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/44 (2.3%)		4/41 (9.8%)		0/36 (0%)		0/49 (0%)
Gastrointestinal disorders
Gastrointestinal necrosis	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Inguinal hernia, obstructive	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Pancreatitis	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Small intestinal obstruction	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Umbilical hernia, obstructive	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Hepatobiliary disorders
Bile duct stone	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Cholecystitis acute	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Cholelithiasis	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Infections and infestations
Pseudomembranous colitis	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Investigations
Alanine aminotransferase increased	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/44 (2.3%)		0/41 (0%)		0/36 (0%)		0/49 (0%)
Psychiatric disorders
Anxiety	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Insomnia	0/44 (0%)		1/41 (2.4%)		0/36 (0%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	Prior Aripiprazole/Escitalopram Combination Therapy		Prior Escitalopram		Prior Aripiprazole		Prior Single-blind Escitalopram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/44 (40.9%)		27/41 (65.9%)		33/36 (91.7%)		31/49 (63.3%)
Gastrointestinal disorders
Diarrhoea	1/44 (2.3%)		0/41 (0%)		3/36 (8.3%)		0/49 (0%)
Nausea	0/44 (0%)		3/41 (7.3%)		7/36 (19.4%)		3/49 (6.1%)
Vomiting	0/44 (0%)		0/41 (0%)		2/36 (5.6%)		0/49 (0%)
General disorders
Fatigue	1/44 (2.3%)		0/41 (0%)		4/36 (11.1%)		4/49 (8.2%)
Investigations
Blood glucose increased	0/44 (0%)		3/41 (7.3%)		0/36 (0%)		0/49 (0%)
Weight increased	2/44 (4.5%)		1/41 (2.4%)		3/36 (8.3%)		2/49 (4.1%)
Nervous system disorders
Akathisia	2/44 (4.5%)		4/41 (9.8%)		3/36 (8.3%)		6/49 (12.2%)
Dizziness	3/44 (6.8%)		1/41 (2.4%)		3/36 (8.3%)		2/49 (4.1%)
Headache	1/44 (2.3%)		2/41 (4.9%)		2/36 (5.6%)		5/49 (10.2%)
Sedation	1/44 (2.3%)		2/41 (4.9%)		0/36 (0%)		5/49 (10.2%)
Somnolence	4/44 (9.1%)		2/41 (4.9%)		3/36 (8.3%)		2/49 (4.1%)
Psychiatric disorders
Anxiety	1/44 (2.3%)		3/41 (7.3%)		2/36 (5.6%)		0/49 (0%)
Insomnia	1/44 (2.3%)		3/41 (7.3%)		0/36 (0%)		0/49 (0%)
Restlessness	1/44 (2.3%)		3/41 (7.3%)		1/36 (2.8%)		2/49 (4.1%)

Limitations/Caveats

The study was terminated early due to Sponsor decision; no safety issues.

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.