The Effects of Quetiapine XR on Cognition, Mood and Anxiety Symptoms in SSRI-Resistant Unipolar Depression
Primary Purpose
Unipolar Depression
Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Quetiapine XR
Sponsored by
About this trial
This is an interventional treatment trial for Unipolar Depression focused on measuring Depression, SSRI, Atypical Antipsychotic, Cognition, Mood, Quality of Life
Eligibility Criteria
Inclusion Criteria:
- Provision of written informed consent
- A diagnosis of Unipolar Depression by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV-TR)
- Females and males aged 19-65 years
- Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment
- Able to understand and comply with the requirements of the study
- Minimum 21-item HAM-D GRID score of 15
- Prior treatment with therapeutic doses of an SSRI-type antidepressant for at least 6 weeks
- Unsatisfactory response to treatment, as determined by clinician, for at least 6 weeks.
Exclusion Criteria:
- Pregnancy or lactation
- Any DSM-IV Axis I disorder not defined in the inclusion criteria
- English as a second language
- Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
- Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator
- Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
- Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
- Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
- Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
- Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
- Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
- Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator
- Involvement in the planning and conduct of the study
- Previous enrolment or randomisation of treatment in the present study.
- Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
- Previous head injury, associated with loss of consciousness.
- Neurological disorder.
- Significant physical health problem
- An absolute neutrophil count (ANC) of 1.5 x 109 per liter;
A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
- Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) >8.5%.
- Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
- Not under physician care for DM
- Physician responsible for patient's DM care has not indicated that patient's DM is controlled.
- Physician responsible for patient's DM care has not approved patient's participation in the study. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomization. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks.
- Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
Sites / Locations
- University of British Columbia Hospital
Arms of the Study
Arm 1
Arm Type
Active Comparator
Arm Label
1
Arm Description
All patients will receive Quetiapine XR at an initial dose of 50mg/day to be increased incrementally (dose of 50mg/day 2 and 150mg/day 3) to achieve a target dose of 300 mg/day by day 4. Tablets will be self-administered early each night.
Outcomes
Primary Outcome Measures
Primary outcome will be measurements of cognitive function, determined both prior to treatment and after 8 weeks of treatment.
Secondary Outcome Measures
To evaluate Quetiapine XR compared to placebo, in SSRI-nonresponsive unipolar patients, in treatment of anxiety and depressive symptoms and biomarkers, improving patient's overall quality of life, and to evaluate its safety and tolerability.
Full Information
NCT ID
NCT00517387
First Posted
August 14, 2007
Last Updated
November 12, 2010
Sponsor
University of British Columbia
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT00517387
Brief Title
The Effects of Quetiapine XR on Cognition, Mood and Anxiety Symptoms in SSRI-Resistant Unipolar Depression
Official Title
The Effects of Quetiapine XR on Cognition, Mood and Anxiety Symptoms in SSRI-Resistant Unipolar Depression
Study Type
Interventional
2. Study Status
Record Verification Date
November 2010
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
University of British Columbia
Collaborators
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Recently published work has examined the effects of "atypical antipsychotics" in SSRI-treatment resistant patients. In these studies, patients with unipolar depression who were treated with SSRI's, but not responsive to treatment after 4 or more weeks, were supplemented with an atypical. The atypical antipsychotics were found to diminish depression symptoms, as well as benefit sleep quality.
We propose a similar study with Quetiapine XR, focusing on thinking processes, mood and anxiety. Patients with depression who are SSRI treatment resistant will be treated with Quetiapine. Cognition will be evaluated in the UBC Mood Disorders Clinic two times: first before Quetiapine addition, then after 8 weeks. Depression symptoms and other measurements will be done at the 9 time points: before Quetiapine, and each week after treatment has begun.
The primary purpose of this study is to evaluate the superiority of Quetiapine XR compared to placebo as augmentation therapy in treatment of anxiety and depressive symptoms in SSRI-nonresponsive unipolar patients. Secondarily, we would like to evaluate the safety and tolerability of quetiapine as augmentation therapy in SSRI-nonresponsive unipolar patients.
Detailed Description
This is a double-blind, placebo-controlled study, in which patients will receive treatment of Quetiapine XR for 8 weeks. All patients will receive Quetiapine XR at an initial dose of 50mg/day to be increased incrementally (dose of 50mg/day 2 and 150mg/day 3) to achieve a target dose of 300 mg/day by day 4. Tablets will be self-administered early each night. Patient's results will be compared to their own baseline measurements, in a double-blind fashion.
Recruited patients will be evaluated at nine time points: a baseline prior to treatment (t = -7 days), an assessment one week after treatment has begun (t = 7 days), two weeks after (t = 14 days), three weeks after (t = 21 days), four weeks after (t = 28 days), five weeks after (t = 35 days), six weeks after (t = 42 days), seven weeks after (t = 49 days) and after 8 weeks of treatment (t = 56 days). Evaluation of cognition, mood and anxiety, will be done blind to which time point is being measured.
Basic blood work (fasting blood glucose, lipid screen including triglycerides, urea and electrolytes, cytokines and neuroimmune markers) will performed on each patient both at baseline (t = -7 days) and at t = 56 days. At 4 weeks, blood sample will be taken for fasting plasma glucose, HbA1c and transaminases. At baseline (-7 days) and completion (56 days) a battery of neurocognitive-impairment tests (see Appendix A) will be administered. In addition, the Hamilton Rating Scale for Depression (21-ITEM HAM-D GRID), Montgomery -Asberg Depression Rating Scale (MADRS), Hamilton Ratings Scale for Anxiety (HAM-A), the UKU Side Effect Rating Scale, and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) will also be assessed by the research team.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unipolar Depression
Keywords
Depression, SSRI, Atypical Antipsychotic, Cognition, Mood, Quality of Life
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
64 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
All patients will receive Quetiapine XR at an initial dose of 50mg/day to be increased incrementally (dose of 50mg/day 2 and 150mg/day 3) to achieve a target dose of 300 mg/day by day 4. Tablets will be self-administered early each night.
Intervention Type
Drug
Intervention Name(s)
Quetiapine XR
Intervention Description
All patients will receive Quetiapine XR at an initial dose of 50mg/day to be increased incrementally (dose of 50mg/day 2 and 150mg/day 3) to achieve a target dose of 300 mg/day by day 4. Tablets will be self-administered early each night.
Primary Outcome Measure Information:
Title
Primary outcome will be measurements of cognitive function, determined both prior to treatment and after 8 weeks of treatment.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
To evaluate Quetiapine XR compared to placebo, in SSRI-nonresponsive unipolar patients, in treatment of anxiety and depressive symptoms and biomarkers, improving patient's overall quality of life, and to evaluate its safety and tolerability.
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Provision of written informed consent
A diagnosis of Unipolar Depression by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV-TR)
Females and males aged 19-65 years
Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment
Able to understand and comply with the requirements of the study
Minimum 21-item HAM-D GRID score of 15
Prior treatment with therapeutic doses of an SSRI-type antidepressant for at least 6 weeks
Unsatisfactory response to treatment, as determined by clinician, for at least 6 weeks.
Exclusion Criteria:
Pregnancy or lactation
Any DSM-IV Axis I disorder not defined in the inclusion criteria
English as a second language
Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator
Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator
Involvement in the planning and conduct of the study
Previous enrolment or randomisation of treatment in the present study.
Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
Previous head injury, associated with loss of consciousness.
Neurological disorder.
Significant physical health problem
An absolute neutrophil count (ANC) of 1.5 x 109 per liter;
A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) >8.5%.
Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
Not under physician care for DM
Physician responsible for patient's DM care has not indicated that patient's DM is controlled.
Physician responsible for patient's DM care has not approved patient's participation in the study. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomization. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks.
Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allan Young, MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of British Columbia Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2A1
Country
Canada
12. IPD Sharing Statement
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The Effects of Quetiapine XR on Cognition, Mood and Anxiety Symptoms in SSRI-Resistant Unipolar Depression
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