Efficacy of Seroquel Versus Seroquel With Selective Serotonin Reuptake Inhibitor For Treatment of Depressive Disorder With Psychotic Features

Official Title: “The Efficacy and Tolerability of Seroquel XR Combined With a Selective Serotonin Re-Uptake Inhibitor Versus Seroquel XR Monotherapy in the Acute Treatment of Major Depressive Disorder With Psychotic Features”

The purpose of this study is to compare the efficacy and tolerability of Seroquel monotherapy for the treatment of Major Depression with Psychotic features with Seroquel plus Selective Serotonin Reuptake Inhibitor.

The proposed study is designed to investigate the non-inferiority of treatment of PsyD using monotherapy with quetiapine XR versus combination treatment using quetiapine XR and an SSRI (sertraline or citalopram or escitalopram) during the acute phase of treatment. The primary outcome measures will be the change rates of symptoms of depression (as measured on the Hamilton Rating Scale for Depression [HAM-D-17] and psychosis (as measured on the Brief Psychiatric Rating Scale [BPRS] Positive Symptoms Subscale).

The secondary aim of the study is to assess the safety and efficacy of the combination of quetiapine XR and SSRIs in patients with the diagnosis of PsyD. Metabolic factors including fasting glucose, fasting insulin, and fasting lipids (total cholesterol, HDL, LDL, and triglycerides) will be obtained at screen and at the 8-week endpoint of the study to assess the impact of treatment on the development of risk factors for metabolic syndrome. Measures of cognitive function (MGH Cognitive and Physical Functioning Questionnaire and RBANS) (Fava et al. 2006; Randolph et al. 1998) will be obtained at screen and the 8-week endpoint of the study to assess the impact of treatment on cognitive function.

Intervention(s) in this Clinical Trial

• Drug: Quetiapine monotherapy
  • • Quetiapine XR 100 mg/h.s. will be the starting dose and increased by 100 mg q h.s. q day to a target dose of 300 mg/h.s. by day three and continued on 300 mg/h.s. through week three. Between weeks four and eight, there will be flexible dosing up to 800 mg/h.s. or reductions in doses to no lower than 200 mg/h.s. Incremental increases or decreases in dose will be no more than 100 mg/h.s. over a minimum of one week, unless a patient is unable to tolerate the current dose. Patients unable to tolerate at least 200 mg/h.s. will be discontinued from the study.
• Drug: Quetiapine with SSRI
  • Quetiapine XR 100 mg/h.s. starting dose; increased by 100 mg q h.s. q day; target dose 300 mg/h.s. by day 3; continued on 300 mg/h.s. through week 3. Weeks 4-8: flexible dosing up to 800 mg/h.s. or reductions in doses to no lower than 200 mg/h.s. Sertraline 50 mg/a.m. starting dose; increased to 100 mg/a.m. at week 2; continued on 100 mg/a.m. through week 3. Weeks 4-8: flexible dosing up to 200 mg/a.m. or reductions in doses to no lower than 50 mg/a.m. Citalopram 20 mg/a.m. starting dose; increased to a target dose of 40 mg/a.m. at week 2; continued on 40 mg/a.m. through week 3. Weeks 4-8: flexible dosing up to 60 mg/a.m. or reductions in doses to no lower than 20 mg/a.m. Escitalopram 5 mg/a.m. starting dose; increase to 10 mg/a.m. at week 2 and continued at 10 mg/a.m. through week 3. Weeks 4-8: flexible dosing up to 20 mg/a.m. or reductions in doses to no lower than 5 mg/a.m.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Quetiapine monotherapy
  • Patients assigned to receive Seroquel monotherapy
• Active Comparator: Quetiapine with SSRI
  • Patients assigned to receive both Seroquel and an SSRI

Primary Measures

• Depressive and psychotic symptoms
  • Time Frame: 8 weeks
    Safety Issue?: No

Inclusion Criteria:

• 1. Written informed consent
• 2. Diagnosis of Major Depressive Disorder with Psychotic Features by the DSM-IV
• 3. Females and Males between the ages of 18-85 years.
• 4. 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
• 5. Able to understand and comply with the requirements of the study
• 6. Initial HAM-D-17 score of > 16, both at the screen visit and at the baseline visit.
• 7. Participants must have an initial BPRS score of > 25 and at least one of the following: > 5 for item 1, > 5 for item 5, > 5 for item 8, > 4 for item 9, > 1 for item 10, > 1 for item 11; these BPRS criteria msut be met both at the screen visit and at the baseline visit.
• 8. Participants must have an initial CGI score of > 2, both at the screen visit and at the baseline visit.

Exclusion Criteria:

• 1. Pregnancy or lactation
• 2. Any DSM-IV Axis I disorder not defined in the

  inclusion criteria

• 3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
• 4. Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator
• 5. 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
• 6. 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
• 7. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomization
• 8. Substance or alcohol dependence within the past three months (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
• 9. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
• 10. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• 11. Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension) as judged by the investigator
• 12. Involvement in the planning and conduct of the study
• 13. Previous enrolment or randomization of treatment in the present study.
• 14. Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements
• 15. 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
• 16. An absolute neutrophil count (ANC) of 1.5 x 10^9 per liter
• 17. Patients with a history seizure disorder; unstable physical disorders (cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic);
• or any physical disorder judged to significantly affect central nervous system function.
• 18. Patients who are currently treated with antidepressants other than the selective serotonin reuptake inhibitors, with mood stabilizing or antipsychotic drugs other than quetiapine.
• 19. Patients with known arrhythmias or arrhythmias noted on screening EKG.
• 20. Outpatients with a CGI score of 7.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Massachusetts General Hospital Other

Overall Clinical Trial Officials and Contacts

John Matthews, MD Principal Investigator Massachusetts General Hospital  

Overall Contact: Rita Seabrook 617-724-9142 

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00955474

Study ID Number: 2008P001022

ClinicalTrials.gov Identifier: NCT00955474

Health Authority: United States: Institutional Review Board