Quetiapine Extended Release Depression Symptoms

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Schizophrenia, Depression

Intervention / Treatment
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* Drug: Quetiapine Extended Release
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine Extended Release<br> | Drug: Quetiapine Extended Release<br>* 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<br>* Other names: Seroquel XR™;|
| Active Comparator: Risperidone<br> | Drug: Risperidone<br>* 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.<br>* Other names: Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 of Calgary Depression Scale for Schizophrenia (CDSS) Score. | 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. | 12 week from baseline to last visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 of HAM-D Score | 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. | 12 weeks from baseline to last visit | 
| Change From Baseline to Week 12 of PANSS Score | 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. | 12 weeks from baseline to last visit | 
| - Change From Baseline to Week 12 of Clinical Global Impression (CGI- Severity of Illness) Score | 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 | 12 weeks from baseline to last visit | 
| CGI- Global Improvement Mean Score at Week 12 | 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 | 12week: descriptive statistic of CGI by visit and treatment | 
| Change From Baseline to Week 12 of Drug Attitude Inventory 10 Item Scale (DAI 10) Score | 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 | 12 week from baseline to last visit | 
| Change From Baseline in the Simpson Angus Scale (SAS) Total Score to Week 12 as an Indication of Neurological Side Effects Section | 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. | 12 weeks from baseline to last visit | 
| Concomitant Use of Antidepressive Drugs From Baseline to Week 12 | 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 | 12 week from baseline to last visi | 
| Change From Screening Visit to Week 12 of Prolactin Live | Plasma prolactin live was drawn prior to morning meal at the screening visit at the last visit | 12 week from screening visit to last visit | 
| Body Mass Index (BMI) at Week 12 | 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. | 12 week | 
| Concomitant Use of Antidepressive Drugs From Baseline to Week 12 | 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 | Change of drug use from baseline to last visi | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Depression, Quetiapine