None listed
Conditions
Brief summary
There is emerging that the medication, Quetiapine (trade name: Seroquel) is clinically useful in treating clinically significant depression (major depressive disorder) and in the augmentation of antidepressant medication in this condition and depression that occurs in bipolar disorder (manic-depression). Quetiapine is currently approved for the treatment of schizophrenia and bipolar disorder. This study will look at whether the addition of the medication Quetiapine XR (trade name: Seroquel XR) to standard antidepressant medication is better than antidepressant medication alone in keeping symptoms of depression to a minimum after a clinically beneficial course of electroconvulsive therapy (ECT) within the previous 3 weeks for clinical depression (major depressive disorder). Participation in the study will occur after remission (disappearance) of clinically significant depression has occurred after treatment with ECT, when there has been failure to respond to an adequate trial of at least one antidepressant medication, or when ECT is the preferred treatment. People will be invited to participate in the study if they: are aged 18-65 years ;have been diagnosed as experiencing major depressive disorder; have had a course of ECT completed within the previous 3 weeks, which has led to remission of depression sustained over the last 2 ECT treatments of the ECT course, after failure to respond to an adequate trial of at least one antidepressant medication, or when ECT is the preferred treatment. People will not be able to participate in the study if they are: at immediate risk to themselves or others; dependent on alcohol or other substances, apart from caffeine or nicotine; or have diabetes mellitus that is not stable or well controlled. Women who are pregnant, or may become pregnant, or are lactating during the course of the study, will also not be able to participate in the study. There will be 2 groups of 20 participants, each, in the study. One group will be treated with the medication Quetiapine XR in combination with an antidepressant medication. Another group will be treated with an antidepressant medication alone. The antidepressant medications, either a selective serotonin reuptake inhibitors (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) that has not been previously prescribed, or previously not helpful in preventing relapse of clinically significant depression, will be prescribed by treating doctors. The addition of Quetiapine XR to the antidepressant medication will be randomly determined, so that the study doctors or treating doctors will have no prior knowledge nor influence on whether this medication is added to prescribed antidepressant medication. The dose of Quetiapine XR will range from 50 milligrams to a maximum of 300 milligrams per day, with doses adjusted according to clinical response to, and tolerability of this medication. Psychiatric medications other than the prescribed antidepressant medication or Quetiapine XR, will not be prescribed or permitted during the course of the study. The duration of the study is 6 months, with weekly study visits for the first month and monthly, thereafter for the remaining 5 months. Participants will be asked questions about the presence of depressive symptoms and how they are tolerating their medication, as well as a physical examination as part of each study visit. Participants will have blood tests (clinical chemistry, haematology) prior to commencing the study, and at 1,2,3 and 6 months. Participants will also have a fasting (not having eaten, or drunk anything other than water since midnight) prior to commencing the study, and at 3 and 6 months. Participants will also have a urine drug test and electrocardiogram (ECG) prior to commencement. Participants will be free to withdraw their consent at any stage without affecting or prejudicing their clinical care in any way. In the event of depressive relapse (recurrence of clinically significant depression), participants will be discontinued from study, with alternative treatment arrangements made in consultation with their primary treating medical practitioner.
Interventions
This is a multicentre (St Vincent's Melbourne, The Melbourne Clinic and The Albert Road Clinic) clinical study of patients with a DSM-IV TR MDD, who have failed to respond to an adequate trial of at least one antidepressant (SSRI or SNRI) or when ECT is the preferred treatment.
Randomization will be into two parallel groups of 20 participants (outpatients and/or inpatients) each.
One group will be treated with Quetiapine XR (flexible dose of 50 to 300 mg daily orally, with dose changes determi
This is a multicentre (St Vincent's Melbourne, The Melbourne Clinic and The Albert Road Clinic) clinical study of patients with a DSM-IV TR MDD, who have failed to respond to an adequate trial of at least one antidepressant (SSRI or SNRI) or when ECT is the preferred treatment. Randomization will be into two parallel groups of 20 participants (outpatients and/or inpatients) each. One group will be treated with Quetiapine XR (flexible dose of 50 to 300 mg daily orally, with dose changes determined by CGI-I scores and tolerability) in combination with TAU (SSRI/SNRI not previously prescribed) and the other group with TAU. TAU is determined by the treating clinician’s selection of monotherapy of a single antidepressant (SSRI/SNRI) at therapeutic dosage and not previously associated with failed response/poor tolerability. The dose range of Quetiapine XR will be flexibly adjusted from 50mg to 300 mg orally. Changes in study medication dose are made according to clinical response (continuation of the current dose if HAMD less than or equal to 7 and CGI-I less than or equal to 3 and increase in dose by 100 mg if HAMD > 7 and < 15 and CGI-I > 3) and tolerability (including as measured by SAS (Simpson and Angus, 1970) and LUNSERS (Day et al, 1995).The duration of treatment will be up to 6 months.
Sponsors
St Vincent's Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
*Provision of written informed consent prior to any study specific procedures *A diagnosis of Major Depressive Disorder by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition, Text-Revision (DSM-IV TR) *Males and females aged 18 to 65 years. *HAMD less than or equal to 7 following a course of ECT which produces remission of depression (HAMD = 7) that is sustained over the last two ECT treatments in the course of ECT, after failure to respond to an adequate trial of at least one antidepressant medication (SSRI or SNRI) or when ECT is the preferred treatment. * Completion of acute course of ECT within 3 weeks of baseline. *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.
Exclusion criteria
Any of the following is regarded as a criterion for exclusion from the study: *Pregnancy or lactation *Any DSM-IV Axis I disorder not defined in the inclusion criteria *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 and/or SSRI/SNRI , 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 3A4 inducers in the 14 days preceding enrolment 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/baseline *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. congestive heart failure, angina pectoris, hypertension or clinically relevant abnormal laboratory values) 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 *A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria: a)Unstable DM defined as enrolment glycosylated hemoglobin (HbA1c) >8.5%. b)Admitted to hospital for treatment of 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 indicated that patient’s DM is controlled. e)Physician responsible for patient’s DM care has not approved patient’s participation in the study f)Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomisation. For thiazolidinediones (glitazones) this period should 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 less than or equal to 1.5 x 10 to the 9 per litre
Outcome results
None listed