Official Title: “Randomized, Placebo-Controlled Effectiveness Study of Quetiapine XR in Co-Morbid Depressive and Anxiety Disorders”

This multi-centred study will be conducted at three centres. The design will be a randomized, placebo-controlled, parallel-group one. This investigation will evaluate the efficacy of add-on Quetiapine XR treatment for patients who meet diagnostic criteria for depressive disorders and one or more comorbid anxiety disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2010

The primary objective is to examine the beneficial effect of quetiapine augmentation of first-line antidepressants in refractory depression with co-morbid anxiety, compared to placebo. It is hypothesized that significant improvement on depression and anxiety symptoms will be seen as evidenced by reduction in Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA) scores after the 12 week treatment period for those who received Quetiapine XR augmentation compared to those who received placebo.2.2

Secondary objectives: 1) To establish the tolerability and safety of Quetiapine XR versus Placebo in patients with co-morbid depressive and anxiety disorders;2) To assess and compare the efficacy of Quetiapine XR versus Placebo improving quality of life in patients with co-morbid depressive and anxiety disorders.; 3) To assess and compare the efficacy of Quetiapine XR versus Placebo on clinical measures symptoms associated to co-morbid depressive and anxiety disorders.

Intervention(s) in this Clinical Trial

• Drug: Quetiapine
  • Patients will be initiated on 50 mg of Quetiapine XR and will be titrated to a maximum dose of 600 mg based on response and tolerability. Dosing will be flexible up to Week 8, and then will remain fixed for until the end of the 12 week period.
• Drug: Placebo
  • placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2

Primary Measures

• Hamilton Depression Rating Scale (HAMD-17)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Hamilton Anxiety Scale (HAMA)
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• changes in the quality of life in patients
  • Time Frame: 12 weeks
    Safety Issue?: No
• Efficacy,tolerability and safety of Quetiapine XR versus Placebo on clinical measures symptoms associated to co-morbid depressive and anxiety disorders
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Provision of written informed consent
• Male and female patients must be of 18 to 65 years of age.
• 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 or Women of childbearing potential must have a negative pregnancy test and must, in the investigator's opinion, practice a clinically accepted, reliable method of contraception during this study. Women who are 6-months postmenopausal are not considered women of child-bearing potential.
• A diagnosis of Major Depressive Disorder or Dysthymic Disorder as defined by DSM-IV criteria and failed to respond to at least one first line treatment.The patient must be receiving antidepressant treatment (SSRIs, SNRIs or mitazapine).
• A co-morbid diagnosis of one or more of the following: Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, and Post Traumatic Stress Disorder as defined by DSM-IV criteria
• A minimum score of ≥17 at Baseline on the 17-item HAM-D.
• Able to understand and comply with the requirements of the study

Exclusion Criteria:

• Pregnancy or lactation
• The presence or history of Obsessive Compulsive Disorder.
• The presence or history of Psychotic Disorders, Bipolar Disorders, Mood Disorders with Psychotic Features
• Patients who, in the investigator's judgment, would require treatment with additional psychotherapeutic drugs, electroconvulsive therapy (ECT), or intensive psychotherapy during the course of the study.
• ECT within the preceding 6 months of screening before inclusion.
• Regular, formal psychotherapy (excluding supportive therapy) started within the last 3 months before inclusion.
• 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.
• 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 significant cytochrome P450 inducers in the 14 days preceding enrolment, including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
• Patients who are currently receiving: monoamine oxidase inhibitors, tricyclic antidepressants, oral neuroleptics, or type 1C anti-arrhythmics within two weeks of screening; herbal psychoactive treatments (St. John's Wort, Kava Kava, Gingko Biloba) within two weeks of screening.
• Patients taking SSRIs or SNRIs for less than two weeks or at a less than therapeutic dose prior to enrolment.
• Patients who require concurrent psychotropic medication other than allowed medication specified in protocol.
• Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation.
• Patients who have met DSM-IV criteria for abuse of or dependence on any drug, including alcohol within 3 months prior to screening.
• Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
• Patients with clinically significant abnormalities in hematology, clinical chemistry, urinalysis or ECG at the screening visit.
• 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
• A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:a)Unstable DM (HbA1c) >8.5%, b) hospital admission for DM or DM related illness in past 12 weeks, c)not under physician care for DM, d) physician responsible for patient's DM care has not approved patient's participation in the study,or indicated DM is controlled e)change in dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomisation. For thiazolidinediones (glitazones) this period will not be less than 8 weeks, g)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)
• An absolute neutrophil count (ANC) of <= 1.5 x 10^9 per

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Centre for Addiction and Mental Health

Overall Clinical Trial Officials and Contacts

Arun Ravindran, MD Principal Investigator Centre for Addiction and Mental Health  

Overall Contact: Arun Ravindran, MD 416-535-8501 Arun_Ravindran@camh.net

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00688818

Study ID Number: 183/2007

ClinicalTrials.gov Identifier: NCT00688818

Health Authority: Canada: Health Canada