Trial Outcomes & Findings for To Assess the Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Participants With Major Depressive Disorder (MDD) (NCT NCT01123707)

NCT ID: NCT01123707

Last Updated: 2021-12-22

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 173 participants
• Primary outcome timeframe: From first dose up to 30 days post last dose (Up to approximately 40 weeks)
• Results posted on: 2021-12-22

Participant Flow

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.

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.

Participant milestones

Measure	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.	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.	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.	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.
Overall Study STARTED	44	41	38	50
Overall Study Safety Sample	44	41	36	49
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	44	41	38	50

Reasons for withdrawal

Measure	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.	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.	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.	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.
Overall Study Lost to Follow-up	3	1	3	2
Overall Study Adverse Event	5	7	5	3
Overall Study Sponsor Discontinued Study	30	24	25	40
Overall Study Participant Met Withdrawal Criteria	1	1	0	1
Overall Study Investigator Withdrew Participant	0	1	1	1
Overall Study Subject Withdrew Consent	4	5	1	2
Overall Study Lack of Efficacy	1	2	1	0
Overall Study Subject Met Exclusion Criteria	0	0	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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 n=170 Participants Total of all reporting groups
Age, Continuous	46.1 years STANDARD_DEVIATION 12.0 • n=5 Participants	45.8 years STANDARD_DEVIATION 10.7 • n=7 Participants	48.6 years STANDARD_DEVIATION 10.8 • n=5 Participants	43.4 years STANDARD_DEVIATION 11.3 • n=4 Participants	45.8 years STANDARD_DEVIATION 11.3 • n=21 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	25 Participants n=7 Participants	26 Participants n=5 Participants	33 Participants n=4 Participants	118 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	16 Participants n=7 Participants	10 Participants n=5 Participants	16 Participants n=4 Participants	52 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	24 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants	34 Participants n=7 Participants	32 Participants n=5 Participants	43 Participants n=4 Participants	145 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	24 Participants n=21 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants	31 Participants n=7 Participants	30 Participants n=5 Participants	42 Participants n=4 Participants	136 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants

PRIMARY outcome

Timeframe: From first dose up to 30 days post last dose (Up to approximately 40 weeks)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
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 TEAEs	75.0 percentage of participants	67.3 percentage of participants	54.5 percentage of participants	70.7 percentage of participants
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 STEAEs	0.0 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	9.8 percentage of participants
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 Severe (Grade 3 or Higher) TEAEs	5.6 percentage of participants	2.0 percentage of participants	0.0 percentage of participants	4.9 percentage of participants
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 Discontinuations from the Trial due to TEAEs	13.9 percentage of participants	6.1 percentage of participants	11.4 percentage of participants	17.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=48 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Baseline	3.4 score on a scale Standard Deviation 0.9	3.2 score on a scale Standard Deviation 0.7	3.1 score on a scale Standard Deviation 1.1	3.4 score on a scale Standard Deviation 1.2
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 1	-0.2 score on a scale Standard Deviation 0.6	-0.4 score on a scale Standard Deviation 0.9	-0.0 score on a scale Standard Deviation 0.7	-0.2 score on a scale Standard Deviation 0.6
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 2	-0.4 score on a scale Standard Deviation 0.6	-0.9 score on a scale Standard Deviation 0.9	-0.3 score on a scale Standard Deviation 0.8	-0.3 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 4	-0.6 score on a scale Standard Deviation 1.0	-0.9 score on a scale Standard Deviation 0.9	-0.1 score on a scale Standard Deviation 0.9	-0.5 score on a scale Standard Deviation 0.8
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 6	-0.5 score on a scale Standard Deviation 1.1	-0.9 score on a scale Standard Deviation 0.6	-0.3 score on a scale Standard Deviation 0.8	-0.5 score on a scale Standard Deviation 0.9
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 8	-0.7 score on a scale Standard Deviation 0.9	-0.7 score on a scale Standard Deviation 1.0	-0.3 score on a scale Standard Deviation 0.8	-0.5 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 14	-1.0 score on a scale Standard Deviation 1.2	-0.7 score on a scale Standard Deviation 1.0	-0.3 score on a scale Standard Deviation 1.4	-0.6 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 20	-1.2 score on a scale Standard Deviation 1.1	-0.9 score on a scale Standard Deviation 0.7	-0.6 score on a scale Standard Deviation 0.7	-0.3 score on a scale Standard Deviation 1.0
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 26	-1.0 score on a scale Standard Deviation 1.4	-1.3 score on a scale Standard Deviation 0.8	-0.8 score on a scale Standard Deviation 0.4	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at Week 32	—	-2.0 score on a scale Standard Deviation 1.0	-1.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.	-2.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score Change from Baseline at End of the Study Visit (Week 43 or before)	-0.7 score on a scale Standard Deviation 1.1	-0.9 score on a scale Standard Deviation 1.0	-0.2 score on a scale Standard Deviation 1.1	-0.6 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=48 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 20	-1.0 score on a scale Standard Deviation 1.1	-1.3 score on a scale Standard Deviation 1.3	-0.4 score on a scale Standard Deviation 0.9	-0.3 score on a scale Standard Deviation 1.2
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 26	-0.6 score on a scale Standard Deviation 2.1	-1.0 score on a scale Standard Deviation 1.1	0.0 score on a scale Standard Deviation 1.4	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Baseline	3.3 score on a scale Standard Deviation 1.2	3.2 score on a scale Standard Deviation 1.4	2.8 score on a scale Standard Deviation 1.2	3.1 score on a scale Standard Deviation 1.2
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 1	-0.2 score on a scale Standard Deviation 0.8	-0.6 score on a scale Standard Deviation 1.0	0.1 score on a scale Standard Deviation 0.8	-0.2 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 2	-0.4 score on a scale Standard Deviation 0.7	-1.0 score on a scale Standard Deviation 1.2	-0.2 score on a scale Standard Deviation 0.9	-0.4 score on a scale Standard Deviation 0.9
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 4	-0.2 score on a scale Standard Deviation 1.0	-0.9 score on a scale Standard Deviation 1.5	0.0 score on a scale Standard Deviation 1.1	-0.5 score on a scale Standard Deviation 1.0
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 6	-0.4 score on a scale Standard Deviation 0.9	-1.1 score on a scale Standard Deviation 1.1	-0.1 score on a scale Standard Deviation 0.9	-0.4 score on a scale Standard Deviation 1.3
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 8	-0.3 score on a scale Standard Deviation 0.9	-0.9 score on a scale Standard Deviation 1.5	-0.2 score on a scale Standard Deviation 1.0	-0.4 score on a scale Standard Deviation 1.0
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 14	-0.8 score on a scale Standard Deviation 1.2	-0.9 score on a scale Standard Deviation 1.4	-0.1 score on a scale Standard Deviation 1.8	-0.2 score on a scale Standard Deviation 1.2
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at Week 32	—	0.0 score on a scale Standard Deviation 1.0	0.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.	-1.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.
Mean Change From Baseline in Patient Global Impression - Severity of Depression Scale (PGI-S) Score Change from Baseline at End of Study Visit (Week 43 or before)	-0.3 score on a scale Standard Deviation 1.2	-0.9 score on a scale Standard Deviation 1.5	-0.1 score on a scale Standard Deviation 1.2	-0.3 score on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Up to 40 weeks

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Orthostatic Hypotension (mmHg)	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Weight (kg): Weight Gain >=7%	2 Participants	4 Participants	4 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Weight (kg): Weight Loss >=7%	1 Participants	2 Participants	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Population: 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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Body Weight Baseline	87.0 kg Standard Deviation 24.2	84.7 kg Standard Deviation 22.6	93.0 kg Standard Deviation 27.1	88.3 kg Standard Deviation 23.5
Mean Change From Baseline in Body Weight Change from Baseline at Week 1	0.1 kg Standard Deviation 1.2	0.1 kg Standard Deviation 1.3	0.0 kg Standard Deviation 2.4	0.1 kg Standard Deviation 1.8
Mean Change From Baseline in Body Weight Change from Baseline at Week 2	0.2 kg Standard Deviation 1.4	0.4 kg Standard Deviation 1.5	0.5 kg Standard Deviation 2.6	0.2 kg Standard Deviation 2.1
Mean Change From Baseline in Body Weight Change from Baseline at Week 4	0.4 kg Standard Deviation 1.4	0.2 kg Standard Deviation 2.1	0.3 kg Standard Deviation 3.8	0.4 kg Standard Deviation 2.3
Mean Change From Baseline in Body Weight Change from Baseline at Week 6	0.3 kg Standard Deviation 2.1	0.3 kg Standard Deviation 2.8	0.3 kg Standard Deviation 4.5	0.1 kg Standard Deviation 2.9
Mean Change From Baseline in Body Weight Change from Baseline at Week 8	0.4 kg Standard Deviation 2.7	0.2 kg Standard Deviation 2.7	-0.0 kg Standard Deviation 5.5	-0.5 kg Standard Deviation 3.2
Mean Change From Baseline in Body Weight Change from Baseline at Week 14	0.7 kg Standard Deviation 3.0	0.6 kg Standard Deviation 4.3	2.0 kg Standard Deviation 5.1	-0.9 kg Standard Deviation 4.8
Mean Change From Baseline in Body Weight Change from Baseline at Week 20	0.4 kg Standard Deviation 5.7	1.4 kg Standard Deviation 1.4	3.8 kg Standard Deviation 2.6	2.0 kg Standard Deviation 1.6
Mean Change From Baseline in Body Weight Change from Baseline at Week 26	—	3.3 kg Standard Deviation 0.5	5.7 kg Standard Deviation NA The standard deviation was not evaluable for 1 participant.	1.4 kg Standard Deviation NA The standard deviation was not evaluable for 1 participant.
Mean Change From Baseline in Body Weight Change from Baseline at Week 32	—	—	—	-3.6 kg Standard Deviation NA The standard deviation was not evaluable for 1 participant.
Mean Change From Baseline in Body Weight Change from Baseline at Last Visit (Week 43 or before)	0.1 kg Standard Deviation 4.0	1.0 kg Standard Deviation 3.7	-0.2 kg Standard Deviation 4.7	0.1 kg Standard Deviation 3.1

SECONDARY outcome

Timeframe: Baseline, Week 26 and End of the study visit (Week 43 or before)

Population: 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.

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

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Body Mass Index (BMI) Change from Baseline at Last Visit (Week 43 or before)	-0.1 kg/m^2 Standard Deviation 1.5	0.4 kg/m^2 Standard Deviation 1.7	0.0 kg/m^2 Standard Deviation 2.5	-0.1 kg/m^2 Standard Deviation 1.1
Mean Change From Baseline in Body Mass Index (BMI) Baseline	31.1 kg/m^2 Standard Deviation 7.6	30.7 kg/m^2 Standard Deviation 7.4	33.4 kg/m^2 Standard Deviation 8.6	30.9 kg/m^2 Standard Deviation 8.1
Mean Change From Baseline in Body Mass Index (BMI) Change from Baseline at Week 26	—	1.2 kg/m^2 Standard Deviation 0.2	2.3 kg/m^2 Standard Deviation NA The standard deviation was not evaluable for 1 participant.	0.4 kg/m^2 Standard Deviation NA The standard deviation was not evaluable for 1 participant.

SECONDARY outcome

Timeframe: Up to 40 weeks

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Creatine phosphokinase (CPK), Total (U/L): ≥3 x ULN	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities High-density Lipoprotein (HDL) Cholesterol, Fasting (mg/dL): ≤30	2 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Low-density Lipoprotein (LDL) Cholesterol, Fasting (mg/dL): ≥160	4 Participants	8 Participants	6 Participants	5 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Triglycerides, Fasting (mg/dL): Men ≥160; Women ≥120	14 Participants	25 Participants	24 Participants	16 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Urea Nitrogen (mg/dL); >= 30 mg/dL	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Alanine Aminotransferase [Serum Glutamic Pyruvic Transaminase (SGPT)] [unit(U)/L]: >=3×ULN	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Aspartate Aminotransferase [Serum Glutamic Oxaloacetic Transaminase (SGOT)] (U/L): >=3×ULN	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Uric Acid (mg/dL): Men ≥10.5; Women ≥8.5	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Bilirubin, Total [mg/deciliter(dL)]: ≥2.0	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Cholesterol, Total, Fasting (mg/dL): ≥240	5 Participants	8 Participants	10 Participants	9 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Eosinophils (%): ≥10	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Hematocrit (%): Female ≤32%; Male: ≤37% or 3 point decrease from baseline	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Hemoglobin (g/dL): Men ≤11.5; Women ≤9.5	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Laboratory Test Abnormalities Prolactin [nanograms (ng)/mL]: >1 ULN	1 Participants	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 26, and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Laboratory Test Results: Prolactin Mean Change from Baseline at Week Last Visit (Week 43 or before)	0.30 ng/mL Standard Deviation 3.25	-0.49 ng/mL Standard Deviation 5.57	0.37 ng/mL Standard Deviation 4.37	1.33 ng/mL Standard Deviation 4.71
Mean Change From Baseline in Laboratory Test Results: Prolactin Mean Change from Baseline at Week 8	0.62 ng/mL Standard Deviation 3.26	-1.10 ng/mL Standard Deviation 6.88	0.52 ng/mL Standard Deviation 3.94	0.31 ng/mL Standard Deviation 4.37
Mean Change From Baseline in Laboratory Test Results: Prolactin Mean Change from Baseline at Week 26	—	-0.75 ng/mL Standard Deviation 0.52	-0.79 ng/mL Standard Deviation NA The standard deviation was not evaluable for 1 participant.	-2.75 ng/mL Standard Deviation NA The standard deviation was not evaluable for 1 participant.

SECONDARY outcome

Timeframe: Baseline, Week 8, and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	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.	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.	Prior Aripiprazole/Escitalopram Combination Therapy n=1 Participants 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.	Prior Escitalopram n=1 Participants 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.
Mean Change From Baseline in Laboratory Test Results: Hemoglobin A1c (HbA1c) Mean Change from Baseline at Week 8	—	—	—	0.30 percentage of HbA1c Standard Deviation NA The standard deviation was not evaluable for 1 participant.
Mean Change From Baseline in Laboratory Test Results: Hemoglobin A1c (HbA1c) Mean Change from Baseline at Last Visit (Week 43 or before)	—	—	-0.30 percentage of HbA1c Standard Deviation NA The standard deviation was not evaluable for 1 participant.	0.30 percentage of HbA1c Standard Deviation NA The standard deviation was not evaluable for 1 participant.

SECONDARY outcome

Timeframe: Up to 40 weeks

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Bradycardia: Decrease of ≥15 bpm	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Sinus Bradycardia: Decrease of ≥15 bpm	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Supraventricular Premature Beat: Not Present to Present	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Ventricular Premature Beat: Not Present to Present	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities 1° Atrioventricular Block: Increase of ≥0.05 second	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Right Bundle-branch Block: Not Present to Present	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Myocardial Ischemia: Not Present to Present	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Symmetrical T-wave Inversion: Not Present to Present	0 Participants	0 Participants	3 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcB	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcF	2 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTcN	1 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 40 weeks

Population: 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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Number of Participants With Potentially Clinically Significant Physical Examination Findings	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Baseline	0.1 score on a scale Standard Deviation 0.3	0.1 score on a scale Standard Deviation 0.3	0.1 score on a scale Standard Deviation 0.5	0.0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at Week 4	0.0 score on a scale Standard Deviation 0.2	0.2 score on a scale Standard Deviation 1.1	-0.1 score on a scale Standard Deviation 0.5	-0.0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at Week 8	0.0 score on a scale Standard Deviation 0.0	-0.1 score on a scale Standard Deviation 0.4	-0.1 score on a scale Standard Deviation 0.6	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at Week 20	0.0 score on a scale Standard Deviation 0.0	-0.2 score on a scale Standard Deviation 0.6	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at Week 26	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at Week 32	—	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation NA Standard deviation was not estimable for 1 participant.	0.0 score on a scale Standard Deviation NA Standard deviation was not estimable for 1 participant.
Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score Change from Baseline at End of Study Visit (Week 43 or before)	-0.0 score on a scale Standard Deviation 0.4	-0.0 score on a scale Standard Deviation 0.3	-0.0 score on a scale Standard Deviation 0.5	-0.0 score on a scale Standard Deviation 0.2

SECONDARY outcome

Timeframe: Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score Baseline	10.3 score on a scale Standard Deviation 0.7	10.1 score on a scale Standard Deviation 0.5	10.1 score on a scale Standard Deviation 0.3	10.0 score on a scale Standard Deviation 0.2
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at Week 4	0.0 score on a scale Standard Deviation 0.7	0.1 score on a scale Standard Deviation 0.5	0.0 score on a scale Standard Deviation 0.3	0.3 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at Week 8	-0.1 score on a scale Standard Deviation 0.7	-0.0 score on a scale Standard Deviation 1.0	-0.1 score on a scale Standard Deviation 0.4	0.2 score on a scale Standard Deviation 0.5
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at Week 20	-0.3 score on a scale Standard Deviation 0.7	-0.3 score on a scale Standard Deviation 0.6	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at Week 26	0.0 score on a scale Standard Deviation 0.0	-0.3 score on a scale Standard Deviation 0.8	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at Week 32	—	-0.7 score on a scale Standard Deviation 1.2	0.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.	0.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.
Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score Change from Baseline at End of Study Visit (Week 43 or before)	0.1 score on a scale Standard Deviation 1.1	-0.0 score on a scale Standard Deviation 0.5	0.1 score on a scale Standard Deviation 1.1	0.3 score on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: Baseline; Weeks 1, 2, 4, 6, 8, 14, 20, 26, 32 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score Baseline	0.4 score on a scale Standard Deviation 0.8	0.1 score on a scale Standard Deviation 0.4	0.2 score on a scale Standard Deviation 0.5	0.1 score on a scale Standard Deviation 0.4
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score Change from Baseline at Week 4	0.0 score on a scale Standard Deviation 0.8	0.2 score on a scale Standard Deviation 0.6	0.1 score on a scale Standard Deviation 0.6	0.3 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score Change from Baseline at Week 8	-0.1 score on a scale Standard Deviation 1.1	-0.0 score on a scale Standard Deviation 0.6	-0.1 score on a scale Standard Deviation 0.6	0.3 score on a scale Standard Deviation 1.0
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score Change from Baseline at Week 20	-0.4 score on a scale Standard Deviation 1.0	-0.3 score on a scale Standard Deviation 0.9	-0.1 score on a scale Standard Deviation 0.4	-0.2 score on a scale Standard Deviation 0.4
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score Change from Baseline at Week 26	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.0	-0.2 score on a scale Standard Deviation 0.4	-0.5 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score Change from Baseline at Week 32	—	-0.3 score on a scale Standard Deviation 0.6	0.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.	-1.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.
Mean Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Clinical Assessment of Akathisia (Item 4) Score Change from Baseline at End of Study Visit (Week 43 or before)	-0.1 score on a scale Standard Deviation 1.1	0.0 score on a scale Standard Deviation 0.5	-0.0 score on a scale Standard Deviation 0.6	0.3 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline; Weeks 1, 2, 4, 6, 8, 14 and Last Visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Baseline	8.3 percentage of participants	4.1 percentage of participants	0.0 percentage of participants	12.2 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Week 1	2.8 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	2.4 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Week 2	2.8 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	2.4 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Week 4	2.8 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	4.9 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Week 6	2.8 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	4.9 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Week 8	2.8 percentage of participants	2.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Week 14	0.0 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	0.0 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 1: Last Visit (Week 43 or before)	5.6 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	2.4 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 2: Week 8	0.0 percentage of participants	2.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 2: Week 14	0.0 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	0.0 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 2: Last Visit (Week 43 or before)	2.8 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 3: Week 14	0.0 percentage of participants	0.0 percentage of participants	2.3 percentage of participants	0.0 percentage of participants
Percentage of Participants With Suicidal Ideation in Each Item as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) Question 3: Last Visit (Week 43 or before)	2.8 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=44 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question a: Baseline	4.4 score on a scale Standard Deviation 1.4	3.6 score on a scale Standard Deviation 1.6	4.2 score on a scale Standard Deviation 1.7	3.8 score on a scale Standard Deviation 1.5
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question a: Change from Baseline at Week 8	-0.4 score on a scale Standard Deviation 0.8	-0.3 score on a scale Standard Deviation 1.1	-0.1 score on a scale Standard Deviation 1.3	-0.4 score on a scale Standard Deviation 0.9
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question a: Change from Baseline at Week 26	-0.4 score on a scale Standard Deviation 1.1	0.0 score on a scale Standard Deviation 0.0	-0.2 score on a scale Standard Deviation 0.4	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question a: Change from Baseline at End of Study Visit (Week 43 or before)	-0.4 score on a scale Standard Deviation 1.2	-0.4 score on a scale Standard Deviation 1.2	-0.1 score on a scale Standard Deviation 1.1	-0.3 score on a scale Standard Deviation 1.1
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question b: Baseline	4.1 score on a scale Standard Deviation 1.4	3.5 score on a scale Standard Deviation 1.6	3.9 score on a scale Standard Deviation 1.7	3.7 score on a scale Standard Deviation 1.5
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question b: Change from Baseline at Week 8	-0.1 score on a scale Standard Deviation 0.9	-0.3 score on a scale Standard Deviation 0.9	0.0 score on a scale Standard Deviation 0.9	-0.2 score on a scale Standard Deviation 0.9
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question b: Change from Baseline at Week 26	0.0 score on a scale Standard Deviation 1.2	-0.2 score on a scale Standard Deviation 0.4	0.2 score on a scale Standard Deviation 0.4	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question b: Change from Baseline at End of Study Visit (Week 43 or before)	-0.2 score on a scale Standard Deviation 1.0	-0.3 score on a scale Standard Deviation 1.1	0.1 score on a scale Standard Deviation 0.8	-0.3 score on a scale Standard Deviation 1.0
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question c: Baseline	4.1 score on a scale Standard Deviation 1.5	3.5 score on a scale Standard Deviation 1.6	4.0 score on a scale Standard Deviation 1.7	3.8 score on a scale Standard Deviation 1.5
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question c: Change from Baseline at Week 8	-0.1 score on a scale Standard Deviation 0.9	-0.2 score on a scale Standard Deviation 0.9	-0.1 score on a scale Standard Deviation 1.0	-0.3 score on a scale Standard Deviation 1.1
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question c: Change from Baseline at Week 26	-0.2 score on a scale Standard Deviation 1.3	-0.2 score on a scale Standard Deviation 0.4	-0.2 score on a scale Standard Deviation 1.1	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question c: Change from Baseline at End of Study Visit (Week 43 or before)	0.0 score on a scale Standard Deviation 1.1	-0.1 score on a scale Standard Deviation 1.1	-0.0 score on a scale Standard Deviation 1.0	-0.4 score on a scale Standard Deviation 1.1
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question d: Baseline	3.6 score on a scale Standard Deviation 1.3	2.9 score on a scale Standard Deviation 1.3	2.5 score on a scale Standard Deviation 1.2	3.0 score on a scale Standard Deviation 1.4
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question d: Change from Baseline at Week 8	-0.4 score on a scale Standard Deviation 0.5	-0.2 score on a scale Standard Deviation 0.4	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation 0.5
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question d: Change from Baseline at Week 26	0.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.	0.0 score on a scale Standard Deviation 0.0	0.0 score on a scale Standard Deviation NA The standard deviation was not evaluable for 1 participant.	0.5 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question d: Change from Baseline at End of Study Visit (Week 43 or before)	0.1 score on a scale Standard Deviation 0.9	-0.1 score on a scale Standard Deviation 0.8	0.1 score on a scale Standard Deviation 0.3	0.0 score on a scale Standard Deviation 0.5
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question e: Baseline	4.4 score on a scale Standard Deviation 1.3	3.7 score on a scale Standard Deviation 1.6	4.2 score on a scale Standard Deviation 1.7	3.9 score on a scale Standard Deviation 1.6
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question e: Change from Baseline at Week 8	-0.3 score on a scale Standard Deviation 0.8	-0.2 score on a scale Standard Deviation 1.1	-0.1 score on a scale Standard Deviation 1.1	-0.3 score on a scale Standard Deviation 0.8
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question e: Change from Baseline at Week 26	-0.4 score on a scale Standard Deviation 1.1	0.0 score on a scale Standard Deviation 0.6	-0.4 score on a scale Standard Deviation 0.5	0.5 score on a scale Standard Deviation 0.7
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question e: Change from Baseline at End of Study Visit (Week 43 or before)	-0.3 score on a scale Standard Deviation 1.4	-0.3 score on a scale Standard Deviation 1.4	-0.1 score on a scale Standard Deviation 0.9	-0.3 score on a scale Standard Deviation 1.2
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question f: Baseline	3.4 score on a scale Standard Deviation 1.1	3.6 score on a scale Standard Deviation 1.2	3.3 score on a scale Standard Deviation 0.9	3.5 score on a scale Standard Deviation 1.2
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question f: Change from Baseline at Week 8	0.2 score on a scale Standard Deviation 1.1	-0.7 score on a scale Standard Deviation 1.7	0.1 score on a scale Standard Deviation 1.1	-0.3 score on a scale Standard Deviation 1.1
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question f: Change from Baseline at Week 26	0.4 score on a scale Standard Deviation 1.9	-0.8 score on a scale Standard Deviation 1.3	-1.0 score on a scale Standard Deviation 0.7	0.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Each Item as Measured by Massachusetts General Hospital Sexual Functioning Inventory (MGH SFI) Subscale Score Question f: Change from Baseline at End of Study Visit (Week 43 or before)	-0.0 score on a scale Standard Deviation 1.6	-0.6 score on a scale Standard Deviation 1.5	-0.0 score on a scale Standard Deviation 1.0	-0.2 score on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline, Week 8, 26 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=43 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) Overall General Subscore Baseline	47.9 score on a scale Standard Deviation 16.8	52.2 score on a scale Standard Deviation 14.6	49.4 score on a scale Standard Deviation 14.7	50.2 score on a scale Standard Deviation 19.9
Mean Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) Overall General Subscore Change from Baseline at Week 8	6.2 score on a scale Standard Deviation 9.9	9.5 score on a scale Standard Deviation 13.6	0.8 score on a scale Standard Deviation 10.4	3.6 score on a scale Standard Deviation 11.0
Mean Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) Overall General Subscore Change from Baseline at Week 26	6.2 score on a scale Standard Deviation 22.4	4.3 score on a scale Standard Deviation 17.7	0.8 score on a scale Standard Deviation 19.6	-0.5 score on a scale Standard Deviation 2.1
Mean Change From Baseline in Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) Overall General Subscore Change from Baseline at End of Study visit (Week 43 or before)	4.6 score on a scale Standard Deviation 14.3	10.0 score on a scale Standard Deviation 16.5	1.0 score on a scale Standard Deviation 14.1	5.0 score on a scale Standard Deviation 15.4

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=36 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=43 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Total Score Baseline	5.1 score on a scale Standard Deviation 2.7	3.8 score on a scale Standard Deviation 2.1	4.6 score on a scale Standard Deviation 2.6	4.3 score on a scale Standard Deviation 2.7
Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Total Score Change from Baseline at Week 8	-2.0 score on a scale Standard Deviation 2.4	-1.4 score on a scale Standard Deviation 1.8	-1.1 score on a scale Standard Deviation 2.1	-0.8 score on a scale Standard Deviation 1.6
Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Total Score Change from Baseline at Week 26	-2.6 score on a scale Standard Deviation 2.7	-0.7 score on a scale Standard Deviation 4.6	-1.9 score on a scale Standard Deviation 1.6	1.7 score on a scale Standard Deviation 2.4
Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Total Score Change from Baseline at End of Study visit (Week 43 or before)	-1.6 score on a scale Standard Deviation 2.8	-1.6 score on a scale Standard Deviation 2.2	-0.6 score on a scale Standard Deviation 2.1	-0.5 score on a scale Standard Deviation 2.5

SECONDARY outcome

Timeframe: Baseline, Weeks 8, 26 and End of the study visit (Week 43 or before)

Population: 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.

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.

Outcome measures

Measure	Prior Aripiprazole n=34 Participants 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.	Prior Single-blind Escitalopram n=49 Participants 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.	Prior Aripiprazole/Escitalopram Combination Therapy n=43 Participants 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.	Prior Escitalopram n=41 Participants 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.
Mean Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score Baseline	24.4 score on a scale Standard Deviation 5.3	22.0 score on a scale Standard Deviation 6.1	23.0 score on a scale Standard Deviation 6.1	22.1 score on a scale Standard Deviation 6.5
Mean Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score Change from Baseline at Week 8	-2.2 score on a scale Standard Deviation 3.3	-4.8 score on a scale Standard Deviation 7.7	-1.3 score on a scale Standard Deviation 4.1	-1.8 score on a scale Standard Deviation 2.6
Mean Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score Change from Baseline at Week 26	-2.2 score on a scale Standard Deviation 5.6	-2.5 score on a scale Standard Deviation 6.0	-3.8 score on a scale Standard Deviation 3.5	2.0 score on a scale Standard Deviation 0.0
Mean Change From Baseline in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) Total Score Change from Baseline at End of Study Visit (Week 43 or before)	-2.6 score on a scale Standard Deviation 5.0	-3.5 score on a scale Standard Deviation 7.6	-1.0 score on a scale Standard Deviation 4.6	-0.2 score on a scale Standard Deviation 4.8

Adverse Events

Prior Aripiprazole/Escitalopram Combination Therapy

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Prior Escitalopram

Serious events: 4 serious events

Other events: 27 other events

Deaths: 0 deaths

Prior Aripiprazole

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Prior Single-blind Escitalopram

Serious events: 0 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	Prior Aripiprazole/Escitalopram Combination Therapy n=44 participants at risk 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.	Prior Escitalopram n=41 participants at risk 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.	Prior Aripiprazole n=36 participants at risk 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.	Prior Single-blind Escitalopram n=49 participants at risk 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.
Gastrointestinal disorders Gastrointestinal necrosis	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Gastrointestinal disorders Inguinal hernia, obstructive	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Gastrointestinal disorders Pancreatitis	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Gastrointestinal disorders Umbilical hernia, obstructive	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Hepatobiliary disorders Bile duct stone	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Hepatobiliary disorders Cholelithiasis	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Infections and infestations Pseudomembranous colitis	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Investigations Alanine aminotransferase increased	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Metabolism and nutrition disorders Hyperglycaemia	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Psychiatric disorders Anxiety	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Psychiatric disorders Insomnia	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.

Other adverse events

Measure	Prior Aripiprazole/Escitalopram Combination Therapy n=44 participants at risk 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.	Prior Escitalopram n=41 participants at risk 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.	Prior Aripiprazole n=36 participants at risk 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.	Prior Single-blind Escitalopram n=49 participants at risk 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.
Gastrointestinal disorders Diarrhoea	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	8.3% 3/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Gastrointestinal disorders Nausea	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	7.3% 3/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	19.4% 7/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	6.1% 3/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Gastrointestinal disorders Vomiting	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	5.6% 2/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
General disorders Fatigue	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	11.1% 4/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	8.2% 4/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Investigations Blood glucose increased	0.00% 0/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	7.3% 3/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Investigations Weight increased	4.5% 2/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	8.3% 3/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	4.1% 2/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Nervous system disorders Akathisia	4.5% 2/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	9.8% 4/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	8.3% 3/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	12.2% 6/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Nervous system disorders Dizziness	6.8% 3/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.4% 1/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	8.3% 3/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	4.1% 2/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Nervous system disorders Headache	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	4.9% 2/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	5.6% 2/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	10.2% 5/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Nervous system disorders Sedation	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	4.9% 2/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	10.2% 5/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Nervous system disorders Somnolence	9.1% 4/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	4.9% 2/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	8.3% 3/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	4.1% 2/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Psychiatric disorders Anxiety	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	7.3% 3/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	5.6% 2/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Psychiatric disorders Insomnia	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	7.3% 3/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	0.00% 0/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.
Psychiatric disorders Restlessness	2.3% 1/44 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	7.3% 3/41 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	2.8% 1/36 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.	4.1% 2/49 • From first dose of study drug through 30 days post last dose (Up to 40 weeks) 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.

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: clinicaltransparency@otsuka-us.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER