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Seroquel Alone Versus Seroquel With an SSRI for Depression With Psychotic Symptoms

This study has been terminated.
(Seroquel went generic and AstraZeneca halted funding.)
Sponsor:
Information provided by (Responsible Party):
John D. Matthews, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00955474
First received: August 6, 2009
Last updated: March 26, 2013
Last verified: March 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder With Psychotic Features
 Drug: Quetiapine monotherapy
Drug: Quetiapine with SSRI
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Depressive and psychotic symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: September 2008
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Quetiapine monotherapy
Patients assigned to receive Seroquel monotherapy
 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.
Other Name: Quetiapine (generic name): Seroquel (brand name)
Active Comparator: Quetiapine with SSRI
Patients assigned to receive both Seroquel and an SSRI
 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 8: 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.
Other Names:
  • Quetiapine (generic name): Seroquel (brand name)
  • Sertraline (generic name): Zoloft (brand name)
  • Citalopram (generic name): Celexa (brand name)
  • Escitalopram (generic name): Lexapro (brand name)

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00955474

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: John Matthews, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: John D. Matthews, Director of Inpatient Research & Training, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00955474     History of Changes
Other Study ID Numbers: 2008P001022
Study First Received: August 6, 2009
Last Updated: March 26, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Depressive Disorder
Depression
Mental Disorders
Psychotic Disorders
Depressive Disorder, Major
Mood Disorders
Behavioral Symptoms
Schizophrenia and Disorders with Psychotic Features
Citalopram
Sertraline
Serotonin Uptake Inhibitors
Quetiapine
Antidepressive Agents, Second-Generation
 Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on June 13, 2013