Seroquel Alone Versus Seroquel With an SSRI for Depression With Psychotic Symptoms
Condition: Major Depressive Disorder With Psychotic Features
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Mental Disorders; Psychotic Disorders
Intervention: Quetiapine; escitalopram; Sertraline; Citalopram
Intervention description: 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.; Active comparator arm:
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.; Active comparator arm:
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.; Active comparator arm:
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.
Intervention MeSH terms: Quetiapine Fumarate; Citalopram; Sertraline; Escitalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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.