ExAttitude: Quetiapine Extended Release Depression Symptoms

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00640562
• Collaborator: (none)
• Enrollment: 216
• Locations: 21
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Aim of the study is to assess if the new compound Seroquel XR™ is non-inferior to Risperidone, considered as the reference drug for the treatment of depressive symptoms of schizophrenia.

PLEASE NOTE: Seroquel SR and Seroquel XR refer to the same formulation. The SR designation was changed to XR after consultation with FDA.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Depression	Drug: Quetiapine Extended Release; Drug: Risperidone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of Quetiapine Extended-Release (Seroquel XR™) and Risperidone in the Treatment of Depressive Symptoms, in Schizophrenic or Schizoaffective Patients: A Randomized, Open Label, Flexible-dose, Parallel Group, Non Inferiority, 12-week Study
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Quetiapine Extended Release	Drug: Quetiapine Extended Release; Uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day; Other Names: Seroquel XR™
Active Comparator: Risperidone	Drug: Risperidone; Uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.; Other Names: Risperdal

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 12 of Calgary Depression Scale for Schizophrenia (CDSS) Score. [12 week from baseline to last visit]

   The CDSS scale is used to assess the level of depression in schizophrenia and to estimate the severity of depressive symptoms. CDSS has 9 items rated on four-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Anchor point descriptions are provided to aid differentiation between each item score. The first eight items are rated on basis of patients' responses to questions; the 9 item is based on clinician's assessment. The sum score is derived by adding the point score of all items (from 0 to 27 points); total score 4-5 is considered for minor depression and 6-7 score for major depression.

Secondary Outcome Measures

1. Change From Baseline to Week 12 of HAM-D Score [12 weeks from baseline to last visit]

   21-item scale for depression. Symptoms are rated finely (on a 5-point scale: absent; doubtful or trivial; mild: moderate severe) or coarsely (on a 3- point scale: absent; doubtful or mild; obvious, distinct, or severe).Total score range 0- 66, higher values represent worse outcome.Number of participants refers to valid for efficacy per protocol. Change:total score at week 12 minus total score at baseline.

2. Change From Baseline to Week 12 of PANSS Score [12 weeks from baseline to last visit]

   30-item scale where each symptom is rated on a severity ranging from 1-7. Symptoms are categorized into 7 items referring to positive, 7 items referring to negative and 16 general psychotic. Total score range 30- 210, higher values represent worse outcome. Number of participants analyzed refers to valid for efficacy per protocol population.

3. - Change From Baseline to Week 12 of Clinical Global Impression (CGI- Severity of Illness) Score [12 weeks from baseline to last visit]

   The CGI-S subset ranges from 1 to 7 such that a score of 1 indicates "normal, not at all ill", while a score of 7 indicates "among the most extremely ill of patients". The change from start of treatment (baseline V2) in the Severity of Illness will be calculated by subtracting the score at start of treatment (baseline V2) from the following visits

4. CGI- Global Improvement Mean Score at Week 12 [12week: descriptive statistic of CGI by visit and treatment]

   The CGI-S subset ranges from 1 to 7 such that a score of 1 indicates "normal, not at all ill", while a score of 7 indicates "among the most extremely ill of patients". The change from start of treatment (baseline V2) in the Severity of Illness will be calculated by subtracting the score at start of treatment (baseline V2) from the following visits

5. Change From Baseline to Week 12 of Drug Attitude Inventory 10 Item Scale (DAI 10) Score [12 week from baseline to last visit]

   These items are presented as self-report statements with which the patient agrees or disagrees. Each response is scored as +1 if correct or -1 if incorrect. The final score is the grand total of the positive and negative points. A positive score means a positive subjective response. A negative total score means a negative subjective response

6. Change From Baseline in the Simpson Angus Scale (SAS) Total Score to Week 12 as an Indication of Neurological Side Effects Section [12 weeks from baseline to last visit]

   Extrapyramidal Side Effects (EPS) will be assessed using the Simpson-Angus Scale (SAS; Simpson GN et al 1970) . The CRF is source data for these assessments and day 0 is considered as baseline. The SAS scale, containing 10 items, will be rated on a five-point scale where 0 is normal and 4 are severe symptoms. Min score =0, max score 40 Change from start of treatment (day 0) will be calculated as the visit score minus the score at start of treatment for each of the neurological assessments.

7. Concomitant Use of Antidepressive Drugs From Baseline to Week 12 [12 week from baseline to last visi]

   Number of concomitant users of antidepressive drugs during the study; the number of participants analyzed refers to safety population, that is to overall participants excluding 6 participants who did not assume any study drug administration

8. Change From Screening Visit to Week 12 of Prolactin Live [12 week from screening visit to last visit]

   Plasma prolactin live was drawn prior to morning meal at the screening visit at the last visit

9. Body Mass Index (BMI) at Week 12 [12 week]

   Patient weight and height have been be collected in order to assess the Body Mass Index (BMI). The mean BMI values reported are assessed after 12 weeks of treatment.

10. Concomitant Use of Antidepressive Drugs From Baseline to Week 12 [Change of drug use from baseline to last visi]

    Number of concomitant users of antidepressive drugs during the study; the number of participants analyzed refers to ITT/safety population, that is to overall participants excluding the 6 participants who did not assume any study drug administration

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of written informed consent

• Patients who satisfy the criteria for diagnosis of schizophrenia or schizoaffective disorder according to DSM-IVTR

• Baseline depressive symptoms, assessed by means of HAM-D (21-item) score ≥20, and HAM-D item 1 score ≥2

Exclusion Criteria:

• Any DSM-IV Axis I disorder other than schizophrenia and schizoaffective disorder

• Patients treated with depot antipsychotic medications within 1 dosing interval before day 0; patients treated with other AP oral medications during the trial except for the switch period

• Use of Clozapine within 28 days prior to enrollment or Clozapine non responders

• Any significant clinical disorder that, in the opinion of the investigator, made the subject unsuitable to be given treatment with an investigational drug

• An absolute neutrophil count (ANC) of ≤1.5 x 109 per liter

• Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fermo	AP	Italy
2	Research Site	Bergamo	BG	Italy
3	Research Site	Brindisi	BR	Italy
4	Research Site	Carbonia	CA	Italy
5	Research Site	Termoli	CB	Italy
6	Research Site	Aversa	CE	Italy
7	Research Site	Catania	CT	Italy
8	Research Site	Nicosia	EN	Italy
9	Research Site	Lido Di Camaiore	LU	Italy
10	Research Site	Messina	ME	Italy
11	Research Site	Milazzo	ME	Italy
12	Research Site	Monza	MI	Italy
13	Research Site	Nocera Inferiore	SA	Italy
14	Research Site	Vallo Della Lucania	SA	Italy
15	Research Site	La Spezia	SP	Italy
16	Research Site	Collegno	TO	Italy
17	Research Site	Frattaminore		Italy
18	Research Site	Lecco		Italy
19	Research Site	Palermo		Italy
20	Research Site	Partinico		Italy
21	Research Site	Roma		Italy

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Chair: Gino Montagnani, MD, AstraZeneca
• Principal Investigator: Mario diFiorino, Ospedale Unico della Versilia (Lido di Camaiore, Lucca Italy)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00640562
• Other Study ID Numbers: D1443L00031
• First Posted: Mar 21, 2008
• Last Update Posted: Jun 19, 2012
• Last Verified: May 1, 2012

• Keywords provided by AstraZeneca: Schizophrenia; Depression; Quetiapine
• Additional relevant MeSH terms: Depression; Depressive Disorder; Schizophrenia; Risperidone; Quetiapine Fumarate

Study Results

Participant Flow

Recruitment Details	Adult male and female patients. with a diagnosis of schizophrenia or schizoaffective disorder (according to DSM-IVTR criteria). with depressive symptoms HAM-D baseline score ≥ 20. and HAM-D item 1 score ≥2.

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Period Title: Overall Study
STARTED	109	107
COMPLETED	91	81
NOT COMPLETED	18	26

Baseline Characteristics

Arm/Group Title	Seroquel XR	Risperidone	Total
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.	Total of all reporting groups
Overall Participants	107	103	210
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.46 (10.71)	42.08 (11.48)	42.27 (11.10)
Sex: Female, Male (Count of Participants)
Female	51 47.7%	40 38.8%	91 43.3%
Male	56 52.3%	63 61.2%	119 56.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 12 of Calgary Depression Scale for Schizophrenia (CDSS) Score.
Description	The CDSS scale is used to assess the level of depression in schizophrenia and to estimate the severity of depressive symptoms. CDSS has 9 items rated on four-point scale: 0=absent; 1=mild; 2=moderate; 3=severe. Anchor point descriptions are provided to aid differentiation between each item score. The first eight items are rated on basis of patients' responses to questions; the 9 item is based on clinician's assessment. The sum score is derived by adding the point score of all items (from 0 to 27 points); total score 4-5 is considered for minor depression and 6-7 score for major depression.
Time Frame	12 week from baseline to last visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Least Squares Mean (Standard Deviation) [Score on a scale]	7.31 (6.1)	5.53 (6.4)

2. Secondary Outcome

Title	Change From Baseline to Week 12 of HAM-D Score
Description	21-item scale for depression. Symptoms are rated finely (on a 5-point scale: absent; doubtful or trivial; mild: moderate severe) or coarsely (on a 3- point scale: absent; doubtful or mild; obvious, distinct, or severe).Total score range 0- 66, higher values represent worse outcome.Number of participants refers to valid for efficacy per protocol. Change:total score at week 12 minus total score at baseline.
Time Frame	12 weeks from baseline to last visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Mean (Standard Deviation) [Score on scale]	-29.83 (10.13)	-23.02 (10.33)

3. Secondary Outcome

Title	Change From Baseline to Week 12 of PANSS Score
Description	30-item scale where each symptom is rated on a severity ranging from 1-7. Symptoms are categorized into 7 items referring to positive, 7 items referring to negative and 16 general psychotic. Total score range 30- 210, higher values represent worse outcome. Number of participants analyzed refers to valid for efficacy per protocol population.
Time Frame	12 weeks from baseline to last visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Mean (Standard Deviation) [score on scale]	102.26 (24.14)	100.51 (25.65)

4. Secondary Outcome

Title	- Change From Baseline to Week 12 of Clinical Global Impression (CGI- Severity of Illness) Score
Description	The CGI-S subset ranges from 1 to 7 such that a score of 1 indicates "normal, not at all ill", while a score of 7 indicates "among the most extremely ill of patients". The change from start of treatment (baseline V2) in the Severity of Illness will be calculated by subtracting the score at start of treatment (baseline V2) from the following visits
Time Frame	12 weeks from baseline to last visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Least Squares Mean (Standard Deviation) [Score on scale]	-1.50 (1.33)	-1.04 (1.31)

5. Secondary Outcome

Title	CGI- Global Improvement Mean Score at Week 12
Description	The CGI-S subset ranges from 1 to 7 such that a score of 1 indicates "normal, not at all ill", while a score of 7 indicates "among the most extremely ill of patients". The change from start of treatment (baseline V2) in the Severity of Illness will be calculated by subtracting the score at start of treatment (baseline V2) from the following visits
Time Frame	12week: descriptive statistic of CGI by visit and treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Mean (Standard Deviation) [score on a scale]	91 (4.47)	88 (4.55)

6. Secondary Outcome

Title	Change From Baseline to Week 12 of Drug Attitude Inventory 10 Item Scale (DAI 10) Score
Description	These items are presented as self-report statements with which the patient agrees or disagrees. Each response is scored as +1 if correct or -1 if incorrect. The final score is the grand total of the positive and negative points. A positive score means a positive subjective response. A negative total score means a negative subjective response
Time Frame	12 week from baseline to last visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Least Squares Mean (Standard Deviation) [score on scale]	86.38 (4.12)	76.64 (4.70)

7. Secondary Outcome

Title	Change From Baseline in the Simpson Angus Scale (SAS) Total Score to Week 12 as an Indication of Neurological Side Effects Section
Description	Extrapyramidal Side Effects (EPS) will be assessed using the Simpson-Angus Scale (SAS; Simpson GN et al 1970) . The CRF is source data for these assessments and day 0 is considered as baseline. The SAS scale, containing 10 items, will be rated on a five-point scale where 0 is normal and 4 are severe symptoms. Min score =0, max score 40 Change from start of treatment (day 0) will be calculated as the visit score minus the score at start of treatment for each of the neurological assessments.
Time Frame	12 weeks from baseline to last visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Mean (Standard Deviation) [score on scale]	2.74 (5.29)	3.88 (5.24)

8. Secondary Outcome

Title	Concomitant Use of Antidepressive Drugs From Baseline to Week 12
Description	Number of concomitant users of antidepressive drugs during the study; the number of participants analyzed refers to safety population, that is to overall participants excluding 6 participants who did not assume any study drug administration
Time Frame	12 week from baseline to last visi

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Number [Participants]	12 11.2%	11 10.7%

9. Secondary Outcome

Title	Change From Screening Visit to Week 12 of Prolactin Live
Description	Plasma prolactin live was drawn prior to morning meal at the screening visit at the last visit
Time Frame	12 week from screening visit to last visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Least Squares Mean (Standard Deviation) [KG]	61.20 (29.77)	90.80 (55.78)

10. Secondary Outcome

Title	Body Mass Index (BMI) at Week 12
Description	Patient weight and height have been be collected in order to assess the Body Mass Index (BMI). The mean BMI values reported are assessed after 12 weeks of treatment.
Time Frame	12 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Mean (Standard Deviation) [Kg/m^2]	29.07 (6.65)	28.80 (5.31)

11. Secondary Outcome

Title	Concomitant Use of Antidepressive Drugs From Baseline to Week 12
Description	Number of concomitant users of antidepressive drugs during the study; the number of participants analyzed refers to ITT/safety population, that is to overall participants excluding the 6 participants who did not assume any study drug administration
Time Frame	Change of drug use from baseline to last visi

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Seroquel XR	Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day	Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
Measure Participants	107	103
Number [Participants]	14 13.1%	17 16.5%

Adverse Events

Arm/Group Title	Seroquel XR		Risperidone
Arm/Group Description	Seroquel XR dose uptitrated starting from 300 mg in the evening on day 0, then increasing to 600 mg and up to 800 mg in the following two evenings. Previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 3 onwards it was possible to adjust the Seroquel XR dose, depending on the clinical response and tolerability of the patient, within the range of 400-800 mg per day		Risperidone dose was uptitrated starting from 1 mg bid (morning and evening) on day 0, then increasing to 2 mg bid and up to 3 mg in the following two days. As per the other arm, previous antipsychotic was taken at the full dose on day 0, half dose on day 1 and stopped from day 2. From day 2 onwards, it was allowed to adjust he dose of Risperidone depending on the clinical response and tolerability of the patient.
All Cause Mortality
	Seroquel XR		Risperidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Seroquel XR		Risperidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/109 (3.7%)		4/107 (3.7%)
Cardiac disorders
Cardiocircolatory Arresti	1/109 (0.9%)		0/107 (0%)
Nervous system disorders
Extrapiramidal Syndrome	0/109 (0%)		1/107 (0.9%)
Faint/Syndrome	1/109 (0.9%)		0/107 (0%)
Psychiatric disorders
Disorientation	0/109 (0%)		1/107 (0.9%)
Psycotic Disorder	0/109 (0%)		1/107 (0.9%)
Delusion	0/109 (0%)		1/107 (0.9%)
Acute Psycosis	1/109 (0.9%)		0/107 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/109 (0.9%)		0/107 (0%)
Social circumstances
Social Stay Hospitalisation	1/109 (0.9%)		0/107 (0%)
Other (Not Including Serious) Adverse Events
	Seroquel XR		Risperidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/ (NaN)		21/ (NaN)
Endocrine disorders
Hyperprolactinemia	1/109 (0.9%)		10/107 (9.3%)
Gastrointestinal disorders
Dry Months	5/109 (4.6%)		0/107 (0%)
General disorders
Asthenia	3/109 (2.8%)		5/107 (4.7%)
Investigations
Weight Increse	3/109 (2.8%)		2/107 (1.9%)
Nervous system disorders
Sedation	5/109 (4.6%)		1/107 (0.9%)
Somnolence	6/109 (5.5%)		2/107 (1.9%)
Vascular disorders
Hypotension	5/109 (4.6%)		1/107 (0.9%)

Limitations/Caveats

Multicentre, randomized, open-label, flexible dose, parallel group, non inferiority

More Information

Certain Agreements

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

The only 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 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.