Active Reference (Fluoxetine) Fixed-dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD)

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02709746
• Collaborator: Takeda (Industry)
• Enrollment: 784
• Locations: 124
• Arms: 4
• Duration (Months): 38.9
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Evaluating the efficacy of vortioxetine 10 mg/day and 20 mg/day versus placebo on depressive symptoms in adolescents (age ≥12 and ≤17 years) with a DSM-5™ (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) diagnosis of Major depressive disorder (MDD).

Condition or Disease	Intervention/Treatment	Phase
Depressive Disorder, Major	Drug: Vortioxetine 10 mg/day; Drug: Vortioxetine 20 mg/day; Drug: Fluoxetine 20 mg/day; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 784 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Interventional, Randomised, Double-blind, Placebo-controlled, Active Reference (Fluoxetine), Fixed-dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years, With Major Depressive Disorder (MDD)
• Study Start Date: May 1, 2016
• Actual Primary Completion Date: Jul 2, 2019
• Actual Study Completion Date: Jul 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vortioxetine 10 mg/day	Drug: Vortioxetine 10 mg/day; 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed; Other Names: Brintellix ® Lu AA21004
Experimental: Vortioxetine 20 mg/day	Drug: Vortioxetine 20 mg/day; 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed; Other Names: Brintellix ® Lu AA21004
Active Comparator: Fluoxetine 20 mg/day,	Drug: Fluoxetine 20 mg/day; 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed
Placebo Comparator: Placebo	Other: Placebo; Encapsulated tablet

Outcome Measures

Primary Outcome Measures

1. Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment [From Randomization to Week 8]

   The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).

Secondary Outcome Measures

1. Change in CDRS-R Total Score During Treatment (at Week 2) [At week 2]

   The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).Children and parents answer separately. Rater judges and selects 'Best'.

2. Change in CDRS-R Total Score During Treatment (at Week 4) [At week 4]

   The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).

3. Change in CDRS-R Total Score During Treatment (at Week 6) [At week 6]

   The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).

4. Change in CDRS-R Mood Score [From randomization to Week 8]

   Change in Children Depression Rating Scale - Revised (CDRS-R) Mood. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Mood is one of four subscores defined in the CDRS-R: sum of items 8, 11, 14, 15; score range 4 to 28. The highest possible score indicates the most severe measure of depression.

5. Change in CDRS-R Somatic Score [From Randomization to Week 8]

   Change in Children Depression Rating Scale - Revised (CDRS-R): Somatic. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Somatic is one of four subscores defined in the CDRS-R: sum of items 4, 5, 6, 7, 16, 17; score ranges from 6 to 36. The highest possible score indicates the most severe measure of depression.

6. Change in CDRS-R Subjective Score [From Randomization to Week 8]

   Change in Children Depression Rating Scale - Revised (CDRS-R): Subjective. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Subjective is one of four subscores defined in the CDRS-R: sum of items 9, 10, 12, 13; score ranges from 4 to 28. The highest possible score indicates the most severe measure of depression.

7. Change in CDRS-R Behaviour Score [From Randomization to Week 8]

   Change in Children Depression Rating Scale - Revised (CDRS-R): Behaviour. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. behaviour is one of four subscores defined in the CDRS-R:sum of items 1, 2, 3; score ranges from 3 to 21. The highest possible score indicates the most severe measure of depression.

8. CDRS-R Response [From Randomization to Week 8]

   Children Depression Rating Scale - Response: defined as a >= 50% decrease in CDRS-R total score, calculated as (change from baseline [Randomization])/(baseline value - 17).

9. CDRS-R Remission [From Randomization to Week 8]

   Remission is defined as a CDRS-R total score <= 28.

10. Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents [From randomization to week 8]

    Using the 10-item depression subscale, assessed by parent (PGBI-10D). Change from randomization to Week 8 in GBI Total Parent/Guardian Version Depression score. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.

11. Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child [From randomization to Week 8]

    The GBI 10-item mania scale is a parent- and subject-rated scale designed to screen for manic symptoms in children and adolescents. The 10 items are rated on a scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranges from 0 to 30 points, with high scores indicating greater pathology.

12. Parent Global Assessment-Global Improvement (PGA) Score [From Randomization to Week 8]

    The PGA is a parent-rated variation of the CGI-I to evaluate the severity of the child's symptoms. The PGA reflects assessments of change from Baseline symptoms using a 7 point scale ranging from 1 (very much improved) to 7 (very much worse).

13. Change in Symbol Digit Modalities Test (SDMT) [From Randomization to Week 8]

    The Symbol Digit Modalities Test (SDMT) is a cognitive test designed to assess speed of performance requiring visual perception, spatial decision-making and psychomotor skills. The SDMT consists of 110 geometric symbols that the patient has to substitute with a corresponding digit in a 90-second period. Each correct digit is counted, and the total score ranges from 0 (less than normal functioning) to 110 (greater than normal functioning).

14. Change in Clinical Global Impression Severity of Illness (CGI-S) Score [From Randomization to Week 8]

    The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients).

15. Clinical Global Impression - Global Improvement (CGI-I) Score [From Randomization to Week 8]

    The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.

16. CGI-S Remission [From Randomization to Week 8]

    Remission defined as CGI-S score of 1 or 2.

17. Change in Children's Global Assessment Scale (CGAS) Score [From Randomization to Week 8]

    The Children's Global Assessment Score (CGAS) is a rating scale which measures psychological, social and school functioning for children. The CGAS is a clinician-rated global scale to measure the lowest level of functioning for a child (4 to 16 years) during a specified time period. The CGAS contains behaviourally oriented descriptors at each anchor point that depict behaviours and life situations applicable to a child. The items range in value from 1 (most functionally impaired child) to 100 (the healthiest). A total score above 70 indicates normal function.

18. Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score [From Randomization to Week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.

19. Change in PedsQL VAS: Sad or Blue (Sadness) Score [From Randomization to Week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.

20. Change in PedsQL VAS: Angry Score [From Randomization to Week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.

21. Change in PedsQL VAS: Worry Score [From Randomization to Week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.

22. Change in PedsQL VAS: Tired (Fatigue) Score [From Randomization to week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.

23. Change in PedsQL VAS: Pain or Hurt Score [From Randomization to Week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.

24. Change in PedsQL VAS Total Average Score [From Randomization to week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL™ VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue, and pain using visual analogue scales. The functionality for each domain is measured on a 10cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. The total score is the average of all 6 items. A lower value represents a better outcome.

25. Change in PedsQL Emotional Distress Summary Average Score [From Randomization to week 8]

    The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. The average emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items. A lower value represents a better outcome.

26. Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores [From Randomization to Week 8]

    PQ-LES-Q total score (items 1 to 14). The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), which is used to measure quality of life in adults. The PQ LES Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning (and item 15 allows subjects to summarize their experience in a global rating). Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good). The total score range of item 1-14 (this outcome measurement) is 14 to 70, with higher scores indicating greater satisfaction.

27. Change in PQ-LES-Q Overall Score [From Randomization to Week 8]

    PQ-LES-Q overall evaluation score (item 15). The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning and item 15 allows subjects to summarize their experience in a global rating (this outcome measurement). Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient is a male or female, aged ≥12 and ≤17 years at Screening (patients who turn 18 years during the study will be allowed to continue in the study).

• The patient has Major depressive disorder (MDD), diagnosed according to DSM-5™.

• The patient has a Children Depression Rating Scale - Revised (CDRS-R) total score ≥45 at the Screening Visit and at the Baseline.

• The patient has a Clinical Global Impression - Severity of Illness (CGI-S) score ≥4 at the Screening Visit and at the Baseline

• The patient has provided assent to participation and parent(s)/legal representative (s) signed the Informed Consent Form.

Exclusion Criteria:

• The patient has participated in a clinical study <30 days prior to the Screening Visit.

Other protocol defined inclusion and exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US1369	Dothan	Alabama	United States
2	US1333	Tucson	Arizona	United States
3	US1310	Little Rock	Arkansas	United States
4	US1062	Costa Mesa	California	United States
5	US1387	Downey	California	United States
6	US1114	Escondido	California	United States
7	US1118	Glendale	California	United States
8	US1123	Imperial	California	United States
9	US1160 Renew Behavioral Health, Inc.	Long Beach	California	United States
10	US1368	Orange	California	United States
11	US1370	Panorama City	California	United States
12	US1351	Wildomar	California	United States
13	US1133	Washington	District of Columbia	United States
14	US1217	Gainesville	Florida	United States
15	US1229	Orange City	Florida	United States
16	US1009	Atlanta	Georgia	United States
17	US1313	Marietta	Georgia	United States
18	US1311	Naperville	Illinois	United States
19	US1315	Naperville	Illinois	United States
20	US1103	Oak Brook	Illinois	United States
21	US1386	Wichita	Kansas	United States
22	US1261	Lake Charles	Louisiana	United States
23	US1015	Baltimore	Maryland	United States
24	US1385 Ericksen Research And Development	Clinton	Mississippi	United States
25	US1064	Creve Coeur	Missouri	United States
26	US1314	O'Fallon	Missouri	United States
27	US1266	Saint Charles	Missouri	United States
28	US1312	Berlin	New Jersey	United States
29	US1222	Princeton	New Jersey	United States
30	US1317	New York	New York	United States
31	US1171	Rochester	New York	United States
32	US1190	Staten Island	New York	United States
33	US1051	Cincinnati	Ohio	United States
34	US1054	Cleveland	Ohio	United States
35	US1334	Middleburg Heights	Ohio	United States
36	US1323	Oklahoma City	Oklahoma	United States
37	US1329	Oklahoma City	Oklahoma	United States
38	US1328	Austin	Texas	United States
39	US1320	Plano	Texas	United States
40	US1162	San Antonio	Texas	United States
41	US1308	Orem	Utah	United States
42	US1309	Richmond	Virginia	United States
43	BG1023	Targovishte		Bulgaria
44	BG1025	Varna		Bulgaria
45	CA1036 University of Calgary	Calgary		Canada
46	CA1038	Toronto		Canada
47	CO1003	Barranquilla		Colombia
48	CO1001	Bello		Colombia
49	CO1004	Bogotá		Colombia
50	CO1002	Pereira		Colombia
51	EE1007	Tallinn		Estonia
52	EE1015	Viljandi		Estonia
53	FR1041	Douai		France
54	FR1017	Elancourt		France
55	FR1009	Nantes		France
56	DE1078	Freiburg		Germany
57	DE1034	Mainz		Germany
58	DE1077	Mannheim		Germany
59	DE1081	Maulbronn		Germany
60	DE1076	Tübingen		Germany
61	HU1023	Budapest		Hungary
62	HU1020	Gyula		Hungary
63	IT1075	Cagliari		Italy
64	IT1073	Genova		Italy
65	IT1029	Messina		Italy
66	IT1068	Napoli		Italy
67	IT1074	Padova		Italy
68	IT1070	Pisa		Italy
69	IT1072 Osppedale Bambin gesu	Rome		Italy
70	KR1035	Cheonan		Korea, Republic of
71	UA1037	Gyeongsang		Korea, Republic of
72	KR1032	Seoul		Korea, Republic of
73	KR1038	Seoul		Korea, Republic of
74	LV1002	Jelgava		Latvia
75	LV1008	Liepaja		Latvia
76	LV1009	Riga		Latvia
77	LV1007	Sigulda		Latvia
78	MX1003	Ciudad de mexico		Mexico
79	MX1014	Culiacán		Mexico
80	MX1011	Guadalajara		Mexico
81	MX1013	Guadalajara		Mexico
82	MX1022	Guadalajara		Mexico
83	MX1023	Mazatlán		Mexico
84	MX1001	Nuevo León		Mexico
85	PL1002	Bialystok		Poland
86	PL1050	Gdansk		Poland
87	PL1068	Kielce		Poland
88	PL1057	Lublin		Poland
89	PL1052	Poznan		Poland
90	PL1051	Wroclaw		Poland
91	PL1054	Wąbrzeźno		Poland
92	RU1009	Arkhangel'sk		Russian Federation
93	RU1016	Ekaterinburg		Russian Federation
94	RU1059	Engel's		Russian Federation
95	RU1046	Krasnodar		Russian Federation
96	RU1011	Lipetsk		Russian Federation
97	RU1004	Nizhniy Novgorod		Russian Federation
98	RU1010	Novosibirsk		Russian Federation
99	RU1012	Rostov on Don		Russian Federation
100	RU1044	Rostov-na-Donu		Russian Federation
101	RU1013	Saratov		Russian Federation
102	RU1038	Saratov		Russian Federation
103	RU1030	St.Petersburg		Russian Federation
104	RU1057	Tomsk		Russian Federation
105	RU1048	Tonnel'nyy		Russian Federation
106	RS1006 Clinic of Neurology and Psychiatry for Children and Adolescents	Belgrade		Serbia
107	RS1010	Belgrad		Serbia
108	RS1011	Kragujevac		Serbia
109	RS1003	Niš		Serbia
110	RS1007	Novi Sad		Serbia
111	ZA1019	Cape Town		South Africa
112	ZA1022	Randburg		South Africa
113	ZA1023	Sandton		South Africa
114	ES1041	Alcorcon		Spain
115	ES1044	Madrid		Spain
116	ES1043	Pamplona		Spain
117	ES1018 Hospital de Sabadell	Sabadell		Spain
118	ES1040	Torremolinos		Spain
119	UA1002	Kyiv		Ukraine
120	UA1019	Odessa		Ukraine
121	UA1001	Poltava		Ukraine
122	UA1004	Ternopil'		Ukraine
123	GB1051	Glasgow		United Kingdom
124	GB1047	Liverpool		United Kingdom

Sponsors and Collaborators

• H. Lundbeck A/S
• Takeda

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

• Study Protocol - Jul 5, 2018
• Statistical Analysis Plan - Aug 15, 2019

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT02709746
• Other Study ID Numbers: 12710A; 2008-005354-20
• First Posted: Mar 16, 2016
• Last Update Posted: Aug 19, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by H. Lundbeck A/S: paediatric patients
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Vortioxetine; Fluoxetine

Study Results

Participant Flow

Pre-assignment Detail	Patients who did not fulfil the randomization criteria for the Double-blind treatment (DBT) Period, were withdrawn from the study after the Single-blind treatment (SBT) period. Patients who fulfilled the randomization criteria for the DBT Period, continued into the DBT Period.

Arm/Group Title	Single-blind Treatment, Placebo	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Arm/Group Description	Placebo, encapsulated, orally	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo, encapsulated, orally
Period Title: Phase A (Single-blind Treatment Period)
STARTED	784	0	0	0	0
COMPLETED	616	0	0	0	0
NOT COMPLETED	168	0	0	0	0
Period Title: Phase A (Single-blind Treatment Period)
STARTED	0	147	162	153	154
COMPLETED	0	126	140	138	138
NOT COMPLETED	0	21	22	15	16

Baseline Characteristics

Arm/Group Title	Single-blind Treatment (SBT), Placebo	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo	Total
Arm/Group Description	Single-blind treatment, Placebo (encapsulated, orally) and Brief Psychosocial Intervention (BPI) for 4 weeks	Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Vortioxetine 10 mg/day, encapsulated tablets, orally.	Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Vortioxetine 20 mg/day, encapsulated tablets, orally.	Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Fluoxetine 20 mg/day, encapsulated tablets, orally.	Eligible patients from SBT period (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Placebo, encapsulated tablets, orally.	Total of all reporting groups
Overall Participants	168	147	162	153	154	784
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.7 (1.61)	14.8 (1.66)	14.5 (1.63)	14.8 (1.60)	14.6 (1.60)	14.67 (1.62)
Sex: Female, Male (Count of Participants)
Female	111 66.1%	93 63.3%	97 59.9%	103 67.3%	105 68.2%	509 64.9%
Male	57 33.9%	54 36.7%	65 40.1%	50 32.7%	49 31.8%	275 35.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	3 1.8%	0 0%	4 2.5%	2 1.3%	4 2.6%	13 1.7%
Native Hawaiian or Other Pacific Islander	1 0.6%	0 0%	0 0%	0 0%	0 0%	1 0.1%
Black or African American	37 22%	19 12.9%	19 11.7%	20 13.1%	22 14.3%	117 14.9%
White	108 64.3%	108 73.5%	110 67.9%	112 73.2%	106 68.8%	544 69.4%
More than one race	15 8.9%	17 11.6%	25 15.4%	17 11.1%	21 13.6%	95 12.1%
Unknown or Not Reported	4 2.4%	3 2%	4 2.5%	2 1.3%	1 0.6%	14 1.8%
CDRS-R total score at Enrolment (units on a scale) [Least Squares Mean (Standard Deviation) ]
Least Squares Mean (Standard Deviation) [units on a scale]	61.24 (10.00)	64.82 (9.38)	65.29 (9.73)	64.06 (8.65)	64.02 (8.96)	63.85 (9.46)
CGI-S at Enrolment (units on a scale) [Least Squares Mean (Standard Deviation) ]
Least Squares Mean (Standard Deviation) [units on a scale]	4.82 (0.68)	4.99 (0.77)	5.00 (0.71)	4.97 (0.68)	4.92 (0.69)	4.94 (0.71)

Outcome Measures

1. Primary Outcome

Title	Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment
Description	The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo	Vortioxetine Average (Avg. VOR)
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet	patients are randomized to one of four treatments. Avg.- VOR is a calculation based on the treatment estimates from VOR 10 mg and VOR 20 mg.
Measure Participants	126	139	137	137	265
Least Squares Mean (Standard Error) [units on a scale]	-17.09 (1.27)	-18.94 (1.22)	-21.95 (1.23)	-18.22 (1.22)	-18.01 (0.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine 10 mg/Day, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4702
	Comments
	Method	Mixed Model Repeated Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; -1.94 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine 20 mg/Day, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6373
	Comments
	Method	Mixed Model Repeated Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -3.71 to 2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine 20 mg/Day,, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0152
	Comments
	Method	Mixed Model Repeated Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.73
	Confidence Interval	(2-Sided) 95%; -6.74 to -0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Vortioxetine Average (Avg. VOR)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8778
	Comments
	Method	Mixed Model Repeated Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; -2.41 to 2.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in CDRS-R Total Score During Treatment (at Week 2)
Description	The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).Children and parents answer separately. Rater judges and selects 'Best'.
Time Frame	At week 2

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	145	158	150	153
Least Squares Mean (Standard Error) [units on a scale]	-9.58 (1.02)	-10.15 (0.99)	-10.34 (1.00)	-8.83 (0.98)

3. Secondary Outcome

Title	Change in CDRS-R Total Score During Treatment (at Week 4)
Description	The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).
Time Frame	At week 4

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	137	153	145	149
Least Squares Mean (Standard Error) [units on a scale]	-14.32 (1.14)	-15.03 (1.10)	-16.25 (1.11)	-13.71 (1.09)

4. Secondary Outcome

Title	Change in CDRS-R Total Score During Treatment (at Week 6)
Description	The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression).
Time Frame	At week 6

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	127	145	143	142
Least Squares Mean (Standard Error) [units on a scale]	-15.43 (1.24)	-17.78 (1.19)	-19.20 (1.2)	-16.71 (1.19)

5. Secondary Outcome

Title	Change in CDRS-R Mood Score
Description	Change in Children Depression Rating Scale - Revised (CDRS-R) Mood. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Mood is one of four subscores defined in the CDRS-R: sum of items 8, 11, 14, 15; score range 4 to 28. The highest possible score indicates the most severe measure of depression.
Time Frame	From randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	-5.05 (0.40)	-5.47 (0.38)	-6.53 (0.38)	-5.32 (0.38)

6. Secondary Outcome

Title	Change in CDRS-R Somatic Score
Description	Change in Children Depression Rating Scale - Revised (CDRS-R): Somatic. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Somatic is one of four subscores defined in the CDRS-R: sum of items 4, 5, 6, 7, 16, 17; score ranges from 6 to 36. The highest possible score indicates the most severe measure of depression.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	-5.63 (0.46)	-6.03 (0.44)	-6.79 (0.45)	-5.78 (0.44)

7. Secondary Outcome

Title	Change in CDRS-R Subjective Score
Description	Change in Children Depression Rating Scale - Revised (CDRS-R): Subjective. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Subjective is one of four subscores defined in the CDRS-R: sum of items 9, 10, 12, 13; score ranges from 4 to 28. The highest possible score indicates the most severe measure of depression.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	-2.41 (0.22)	-2.63 (0.21)	-3.23 (0.21)	-2.66 (0.21)

8. Secondary Outcome

Title	Change in CDRS-R Behaviour Score
Description	Change in Children Depression Rating Scale - Revised (CDRS-R): Behaviour. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. behaviour is one of four subscores defined in the CDRS-R:sum of items 1, 2, 3; score ranges from 3 to 21. The highest possible score indicates the most severe measure of depression.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	-4.32 (0.38)	-4.90 (0.36)	-5.52 (0.37)	-4.73 (0.36)

9. Secondary Outcome

Title	CDRS-R Response
Description	Children Depression Rating Scale - Response: defined as a >= 50% decrease in CDRS-R total score, calculated as (change from baseline [Randomization])/(baseline value - 17).
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Count of Participants [Participants]	53 31.5%	60 40.8%	68 42%	49 32%

10. Secondary Outcome

Title	CDRS-R Remission
Description	Remission is defined as a CDRS-R total score <= 28.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Count of Participants [Participants]	21 12.5%	24 16.3%	32 19.8%	20 13.1%

11. Secondary Outcome

Title	Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents
Description	Using the 10-item depression subscale, assessed by parent (PGBI-10D). Change from randomization to Week 8 in GBI Total Parent/Guardian Version Depression score. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome.
Time Frame	From randomization to week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Least Squares Mean (Standard Deviation) [units on a scale]	-6.23 (0.56)	-6.48 (0.54)	-8.00 (0.54)	-6.62 (0.53)

12. Secondary Outcome

Title	Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child
Description	The GBI 10-item mania scale is a parent- and subject-rated scale designed to screen for manic symptoms in children and adolescents. The 10 items are rated on a scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranges from 0 to 30 points, with high scores indicating greater pathology.
Time Frame	From randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	-5.48 (0.61)	-5.55 (0.59)	-6.30 (0.59)	-6.03 (0.58)

13. Secondary Outcome

Title	Parent Global Assessment-Global Improvement (PGA) Score
Description	The PGA is a parent-rated variation of the CGI-I to evaluate the severity of the child's symptoms. The PGA reflects assessments of change from Baseline symptoms using a 7 point scale ranging from 1 (very much improved) to 7 (very much worse).
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	125	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	2.80 (0.10)	2.74 (0.09)	2.49 (0.09)	2.72 (0.09)

14. Secondary Outcome

Title	Change in Symbol Digit Modalities Test (SDMT)
Description	The Symbol Digit Modalities Test (SDMT) is a cognitive test designed to assess speed of performance requiring visual perception, spatial decision-making and psychomotor skills. The SDMT consists of 110 geometric symbols that the patient has to substitute with a corresponding digit in a 90-second period. Each correct digit is counted, and the total score ranges from 0 (less than normal functioning) to 110 (greater than normal functioning).
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	125	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	3.75 (1.02)	2.64 (0.98)	2.69 (0.98)	2.41 (0.97)

15. Secondary Outcome

Title	Change in Clinical Global Impression Severity of Illness (CGI-S) Score
Description	The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients).
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	-1.23 (0.10)	-1.38 (0.10)	-1.59 (0.10)	-1.21 (0.10)

16. Secondary Outcome

Title	Clinical Global Impression - Global Improvement (CGI-I) Score
Description	The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	125	139	137	137
Least Squares Mean (Standard Error) [units on a scale]	2.81 (0.10)	2.69 (0.09)	2.50 (0.09)	2.73 (0.09)

17. Secondary Outcome

Title	CGI-S Remission
Description	Remission defined as CGI-S score of 1 or 2.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	139	137	137
Count of Participants [Participants]	26 15.5%	33 22.4%	36 22.2%	24 15.7%

18. Secondary Outcome

Title	Change in Children's Global Assessment Scale (CGAS) Score
Description	The Children's Global Assessment Score (CGAS) is a rating scale which measures psychological, social and school functioning for children. The CGAS is a clinician-rated global scale to measure the lowest level of functioning for a child (4 to 16 years) during a specified time period. The CGAS contains behaviourally oriented descriptors at each anchor point that depict behaviours and life situations applicable to a child. The items range in value from 1 (most functionally impaired child) to 100 (the healthiest). A total score above 70 indicates normal function.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	126	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	12.24 (1.25)	13.89 (1.20)	16.43 (1.20)	14.52 (1.19)

19. Secondary Outcome

Title	Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-0.47 (0.19)	-0.76 (0.18)	-0.78 (0.18)	-0.71 (0.18)

20. Secondary Outcome

Title	Change in PedsQL VAS: Sad or Blue (Sadness) Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-1.90 (0.26)	-1.71 (0.25)	-2.45 (0.25)	-2.12 (0.24)

21. Secondary Outcome

Title	Change in PedsQL VAS: Angry Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-0.51 (0.23)	-0.70 (0.23)	-1.01 (0.23)	-0.59 (0.23)

22. Secondary Outcome

Title	Change in PedsQL VAS: Worry Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-0.96 (0.25)	-1.17 (0.24)	-0.91 (0.24)	-1.33 (0.24)

23. Secondary Outcome

Title	Change in PedsQL VAS: Tired (Fatigue) Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time Frame	From Randomization to week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-1.18 (0.29)	-1.40 (0.28)	-1.55 (0.28)	-1.27 (0.28)

24. Secondary Outcome

Title	Change in PedsQL VAS: Pain or Hurt Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-1.12 (0.22)	-0.97 (0.21)	-0.83 (0.21)	-0.76 (0.21)

25. Secondary Outcome

Title	Change in PedsQL VAS Total Average Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL™ VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue, and pain using visual analogue scales. The functionality for each domain is measured on a 10cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. The total score is the average of all 6 items. A lower value represents a better outcome.
Time Frame	From Randomization to week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-1.00 (0.17)	-1.13 (0.16)	-1.33 (0.16)	-1.14 (0.16)

26. Secondary Outcome

Title	Change in PedsQL Emotional Distress Summary Average Score
Description	The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue and pain using visual analogue scales. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The patients are asked to mark on the line how they feel. The average emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items. A lower value represents a better outcome.
Time Frame	From Randomization to week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	124	140	138	137
Least Squares Mean (Standard Error) [units on a scale]	-0.93 (0.18)	-1.09 (0.17)	-1.33 (0.17)	-1.18 (0.17)

27. Secondary Outcome

Title	Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores
Description	PQ-LES-Q total score (items 1 to 14). The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), which is used to measure quality of life in adults. The PQ LES Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning (and item 15 allows subjects to summarize their experience in a global rating). Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good). The total score range of item 1-14 (this outcome measurement) is 14 to 70, with higher scores indicating greater satisfaction.
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	125	140	137	137
Least Squares Mean (Standard Error) [units on a scale]	7.62 (0.97)	7.56 (0.93)	9.26 (0.94)	7.06 (0.92)

28. Secondary Outcome

Title	Change in PQ-LES-Q Overall Score
Description	PQ-LES-Q overall evaluation score (item 15). The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning and item 15 allows subjects to summarize their experience in a global rating (this outcome measurement). Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good).
Time Frame	From Randomization to Week 8

Outcome Measure Data

Analysis Population Description

Double-blind treatment period. There where overall numbers of participants analyzed are not consistent with numbers provided in the participant flow can be due to particpant flow module total number of patients also includes patients that were enrolled but not treated and other reasons of discontinuation from the study.

Arm/Group Title	Vortioxetine 10 mg/Day	Vortioxetine 20 mg/Day	Fluoxetine 20 mg/Day,	Placebo
Arm/Group Description	Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed	Fluoxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed	Placebo: Encapsulated tablet
Measure Participants	125	140	137	137
Least Squares Mean (Standard Error) [units on a scale]	0.54 (0.08)	0.43 (0.08)	0.67 (0.08)	0.51 (0.08)

Adverse Events

Time Frame	16 weeks
Adverse Event Reporting Description	There where the total numbers of participants at risk are not onsistent with numbers provided in the particpant flow module is due that patients that were enrolled but not treated are included in the total number in the participant flow module.
Arm/Group Title	SBT, Placebo		DBT, Vortioxetine 10 mg		DBT, Vortioxetine 20 mg		DBT, Fluoxetine 20 mg		DBT, Placebo
Arm/Group Description	Patients not randomized to DBT period		Vortioxetine 10 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed		Vortioxetine 20 mg/day: 20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed		Vortioxetine 20 mg/day: 10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed		Placebo, encapsulated tablet, orally
All Cause Mortality
	SBT, Placebo		DBT, Vortioxetine 10 mg		DBT, Vortioxetine 20 mg		DBT, Fluoxetine 20 mg		DBT, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/777 (0%)		0/147 (0%)		0/161 (0%)		0/153 (0%)		0/154 (0%)
Serious Adverse Events
	SBT, Placebo		DBT, Vortioxetine 10 mg		DBT, Vortioxetine 20 mg		DBT, Fluoxetine 20 mg		DBT, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/777 (1.7%)		4/147 (2.7%)		7/161 (4.3%)		3/153 (2%)		1/154 (0.6%)
Blood and lymphatic system disorders
Lymphadenitis	1/777 (0.1%)	1	0/147 (0%)	0	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Infections and infestations
Appendicitis	1/777 (0.1%)	1	1/147 (0.7%)	1	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Bronchitis viral	0/777 (0%)	0	1/147 (0.7%)	1	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Gastroenteritis	0/777 (0%)	0	1/147 (0.7%)	1	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Gastrointestinal viral infection	0/777 (0%)	0	0/147 (0%)	0	0/161 (0%)	0	0/153 (0%)	0	1/154 (0.6%)	1
Influenza	1/777 (0.1%)	3	0/147 (0%)	0	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Meningitis	0/777 (0%)	0	0/147 (0%)	0	1/161 (0.6%)	1	0/153 (0%)	0	0/154 (0%)	0
Pneumonia bacterial	0/777 (0%)	0	0/147 (0%)	0	1/161 (0.6%)	1	0/153 (0%)	0	0/154 (0%)	0
Viral upper respiratory tract infection	0/777 (0%)	0	0/147 (0%)	0	1/161 (0.6%)	3	0/153 (0%)	0	0/154 (0%)	0
Injury, poisoning and procedural complications
Head injury	0/777 (0%)	0	0/147 (0%)	0	0/161 (0%)	0	1/153 (0.7%)	1	0/154 (0%)	0
Psychiatric disorders
Depression	0/777 (0%)	0	0/147 (0%)	0	1/161 (0.6%)	1	0/153 (0%)	0	0/154 (0%)	0
Generalised anxiety disorder	1/777 (0.1%)	1	0/147 (0%)	0	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Suicidal behaviour	1/777 (0.1%)	1	0/147 (0%)	0	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Suicidal ideation	6/777 (0.8%)	6	1/147 (0.7%)	1	3/161 (1.9%)	4	2/153 (1.3%)	2	0/154 (0%)	0
Suicide attempt	2/777 (0.3%)	2	0/147 (0%)	0	1/161 (0.6%)	1	0/153 (0%)	0	0/154 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	1/777 (0.1%)	1	0/147 (0%)	0	0/161 (0%)	0	0/153 (0%)	0	0/154 (0%)	0
Other (Not Including Serious) Adverse Events
	SBT, Placebo		DBT, Vortioxetine 10 mg		DBT, Vortioxetine 20 mg		DBT, Fluoxetine 20 mg		DBT, Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	128/777 (16.5%)		47/147 (32%)		57/161 (35.4%)		40/153 (26.1%)		30/154 (19.5%)
Gastrointestinal disorders
Diarrhoea	13/777 (1.7%)	14	5/147 (3.4%)	5	9/161 (5.6%)	10	7/153 (4.6%)	11	5/154 (3.2%)	5
Nausea	28/777 (3.6%)	31	21/147 (14.3%)	23	31/161 (19.3%)	48	10/153 (6.5%)	16	7/154 (4.5%)	9
Vomiting	13/777 (1.7%)	13	7/147 (4.8%)	7	15/161 (9.3%)	20	8/153 (5.2%)	10	1/154 (0.6%)	1
Infections and infestations
Nasopharyngitis	26/777 (3.3%)	28	6/147 (4.1%)	7	10/161 (6.2%)	11	10/153 (6.5%)	12	5/154 (3.2%)	7
Nervous system disorders
Dizziness	21/777 (2.7%)	23	11/147 (7.5%)	14	7/161 (4.3%)	7	6/153 (3.9%)	8	5/154 (3.2%)	6
Headache	65/777 (8.4%)	85	23/147 (15.6%)	37	20/161 (12.4%)	46	10/153 (6.5%)	16	12/154 (7.8%)	19

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.