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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
32
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.
Massachusetts General Hospital
Boston, Massachusetts, United States
Depression
Depression measured with Hamilton Rating Scale for Depression 17 (HAM-D) at baseline and 8 weeks. Ham D 17 scores range from 0-52, 52 being the most severe.
Time frame: 8 weeks
Psychosis
Psychosis measured by Brief Psychosis Rating Scale (BPRS) at baseline and 8 weeks. Scores range from 24-168, with 168 bring the most severe.
Time frame: 8 weeks
Fasting Blood Glucose
Fasting glucose levels collected at Baseline and Week 8. Normal range for fasting glucose is 70-110 mg/dl.
Time frame: 8 weeks
CPFQ (Cognitive and Psychological Functioning Questionnaire)
Score on the Cognitive and Psychological Functioning Questionnaire (CPFQ). Scores range from 7-42 with 42 referring to the worst functioning. CPFQ measured at baseline and 8 weeks.
Time frame: 8 weeks
RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Total Score
Neuropsychological Assessment. Scores range from 40-160, with 160 referring to higher cognitive functioning. All RBANS subscales and the total score are standardized using age-based norms. Thus, they have a mean of 100 (average) and a standard deviation of 15. A score of 90-110 is in the average range; score of 70-85 mild to moderate cognitive impairment; score \<70 moderate to severe impairment. RBANS measured at baseline and 8 weeks.
Time frame: 8
RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Immediate Memory Sub-scale Score
RBANS Immediate Memory sub-scale scores at Baseline and Week 8. Scores range from 40-160, with 160 referring to higher cognitive functioning. All RBANS subscales and the total score are standardized using age-based norms. Thus, they have a mean of 100 (average) and a standard deviation of 15. A score of 90-110 is in the average range; score of 70-85 mild to moderate cognitive impairment; score \<70 moderate to severe impairment.
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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.
Time frame: 8 weeks
RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Visuospatial/Constructional Sub-scale.
RBANS Visuospatial/Constructional sub-scales at Baseline and Week 8. Scores range from 40-160, with 160 referring to higher cognitive functioning. All RBANS subscales and the total score are standardized using age-based norms. Thus, they have a mean of 100 (average) and a standard deviation of 15. A score of 90-110 is in the average range; score of 70-85 mild to moderate cognitive impairment; score \<70 moderate to severe impairment.
Time frame: 8 weeks
RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Language Sub-scale Score.
RBANS Language sub-scale scores at Baseline and Week 8 of study. Scores range from 40-160, with 160 referring to higher cognitive functioning. All RBANS subscales and the total score are standardized using age-based norms. Thus, they have a mean of 100 (average) and a standard deviation of 15. A score of 90-110 is in the average range; score of 70-85 mild to moderate cognitive impairment; score \<70 moderate to severe impairment.
Time frame: 8 weeks
RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Attention Sub-scale Scores at Baseline and Week 8.
RBANS Attention sub-scale scores at Baseline and Week 8. Scores range from 40-160, with 160 referring to higher cognitive functioning. All RBANS subscales and the total score are standardized using age-based norms. Thus, they have a mean of 100 (average) and a standard deviation of 15. A score of 90-110 is in the average range; score of 70-85 mild to moderate cognitive impairment; score \<70 moderate to severe impairment.
Time frame: 8 weeks
RBANS (Repeatable Battery for Assessment of Neuropsychological Status) Delayed Memory Subscale Scores at Baseline and Week 8.
RBANS Delayed Memory subscale scores at Baseline and Week 8. Scores range from 40-160, with 160 referring to higher cognitive functioning. All RBANS subscales and the total score are standardized using age-based norms. Thus, they have a mean of 100 (average) and a standard deviation of 15. A score of 90-110 is in the average range; score of 70-85 mild to moderate cognitive impairment; score \<70 moderate to severe impairment.
Time frame: 8 weeks
Blood Level of Total Cholesterol Levels Were Collected at Baseline and Week 8.
Cholesterol levels were collected at Baseline and Week 8. Normal cholesterol levels should be \<200mg/dl.
Time frame: 8 weeks
Blood Level of Triglycerides at Baseline and Week 8.
Level of triglycerides at Baseline and Week 8. Normal range: 40-150mg/dl.
Time frame: 8 weeks
HDL Blood Levels at Baseline and Week 8.
HDL levels at Baseline and Week 8. Normal range: 35-100 mg/dl.
Time frame: 8 weeks
LDL Blood Levels at Baseline and Week 8.
LDL levels at Baseline and Week 8. Normal range \< 100 mg/dl.
Time frame: 8 weeks
Blood Hemoglobin A1C at Baseline and Week 8.
Blood hemoglobin A1C at Baseline and Week 8. Normal range: 3.8%-6.4%.
Time frame: 8 weeks