Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, MDD
Brief summary
The primary purpose of this study is to evaluate whether treatment with (SEROQUEL SR) quetiapine fumarate sustained release (SR) for 9 weeks compared to placebo will improve depressive symptoms in elderly patients with major depressive disorder. PLEASE NOTE: Seroquel SR and Seroquel XR refer to the same formulation. The SR designation was changed to XR after consultation with FDA.
Interventions
DRUGQuetiapine
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
66 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients, 66 years or older, with a documented clinical diagnosis of MDD.
Exclusion criteria
* The presence of dementia or mental disorder other than MDD within 6 months of enrolment, * Uncontrolled hypertension, substance or alcohol abuse * A current diagnosis of cancer or a current or past diagnosis of stroke
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 9. | Baseline to Week 9 | MADRS total score (0-60 units), where lower scores indicate less depressive symptoms, calculated as Week 9 value - baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline for Satisfaction With Medication From Quality of Life, Enjoyment, Satisfaction Questionaire (Q-LES-Q) | Baseline to Week 9 | Item 15 the Quality of Life, Enjoyment Satisfaction Questionnaire (score 1 least -5 best) on Q-LES-Q, calculated as Week 9 value - baseline value |
| Change From Baseline in Anxiety Symptoms Measured by Hamilton Anxiety 14 Item Scale (HAM-A) | Baseline to Week 9 | Change in HAM-A total score (total score 0-56), calculated as Week 9 value - baseline value, where lower scores indicate less anxiety. |
| Change From Baseline in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index | Baseline to Week 9 | The Pittsburgh Sleep Quality Index is an eighteen questionnaire scored with 7 sleep component scores each on a 0 to 3 scale, total score range from 0 to 21, worst value 21, best value 0 |
| Change From Baseline in Health-related Quality of Life, Enjoyment and Satisfaction (Q-LES-Q) | Baseline to Week 9 | Q-LES-Q as percent of maximum (0 to 100%) calculated as Week 9 - baseline, where higher values indicate better quality of life. |
| Change From Baseline in Somatic Symptoms Cluster From the Hamilton Anxiety Scale (HAM-A) | Baseline to Week 9 | The Somatic symptom Cluster of the Hamilton Anxiety Scale is a 7 item cluster associated with somatic symptoms \*somatic muscular, somatic sensory, cardiovascular system, respiratory system, gastrointestinal system, genitourinary system, autonomic system) with a range of values from 0 to 28, worst value 28, best value 0 |
| Tolerability as Measured by Adverse Event Withdrawals During Treatment | Baseline to Week 9 | — |
| Change From Baseline in Suicidal Thoughts as Measured by Montgomery-Asberg Depression Rating Scale (MADRS) Item 10 | Baseline to Week 9 | The suicide item is a single item of the Montgomery-Asberg Depression Rating Scale with a range of values from 0 to 6, worst value 6, best value 0 |
Countries
Argentina, Estonia, Finland, Russia, Ukraine, United States
Participant flow
Recruitment details
International multi-center study, 53 sites recruited between Sept 2006 and Dec 2007
Pre-assignment details
Screening for eligibility and wash-out of restricted medications. At least moderate depression symptoms assessed by the Hamilton Rating Scale for Depression
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine XR Quetiapine fumarate XR - flexibly dosed (50 - 300 mg) | 166 |
| Placebo Placebo | 172 |
| Total | 338 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 6 |
| Overall Study | Did not complete 2-week follow-up visit | 17 | 17 |
| Overall Study | Did not complete 61 days of treatment | 5 | 4 |
| Overall Study | Lack of Efficacy | 1 | 12 |
| Overall Study | Left region | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Study specific Discontinuation Criteria | 0 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 17 |
Baseline characteristics
| Characteristic | Quetiapine XR | Placebo | Total |
|---|---|---|---|
| Age, Customized 66 to 75 years | 135 Participants | 137 Participants | 272 Participants |
| Age, Customized >75 years | 31 Participants | 35 Participants | 66 Participants |
| DSM IV diagnosis 296.2x - Major depressive disorder, single episode | 27 Participants | 25 Participants | 52 Participants |
| DSM IV diagnosis 296.3x - Major depressive disorder, recurrent | 139 Participants | 147 Participants | 286 Participants |
| Region of Enrollment Europe | 124 Participants | 126 Participants | 250 Participants |
| Region of Enrollment North America | 24 Participants | 27 Participants | 51 Participants |
| Region of Enrollment South America | 18 Participants | 19 Participants | 37 Participants |
| Sex: Female, Male Female | 116 Participants | 120 Participants | 236 Participants |
| Sex: Female, Male Male | 50 Participants | 52 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 133 / 166 | 54 / 172 |
| serious Total, serious adverse events | 4 / 166 | 2 / 172 |
Outcome results
Primary
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 9.
MADRS total score (0-60 units), where lower scores indicate less depressive symptoms, calculated as Week 9 value - baseline value.
Time frame: Baseline to Week 9
Population: All randomized patients who took at least one dose of study medication and had at least one post baseline assessment, with last observation carried forward to week 9 for patients who did not complete the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 9. | -16 units on scale | Standard Deviation 8 |
| Placebo | Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score to Week 9. | -9 units on scale | Standard Deviation 8 |
Secondary
Change From Baseline for Satisfaction With Medication From Quality of Life, Enjoyment, Satisfaction Questionaire (Q-LES-Q)
Item 15 the Quality of Life, Enjoyment Satisfaction Questionnaire (score 1 least -5 best) on Q-LES-Q, calculated as Week 9 value - baseline value
Time frame: Baseline to Week 9
Population: All randomized patients who took at least one dose of study medication and had at least one post baseline assessment, with last observation carried forward to week 9 for patients who did not complete the study. Patients not on medication at baseline would have left the item blank and therefore no change from baseline could be calculated
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quetiapine XR | Change From Baseline for Satisfaction With Medication From Quality of Life, Enjoyment, Satisfaction Questionaire (Q-LES-Q) | 0 units on scale |
| Placebo | Change From Baseline for Satisfaction With Medication From Quality of Life, Enjoyment, Satisfaction Questionaire (Q-LES-Q) | 0 units on scale |
Secondary
Change From Baseline in Anxiety Symptoms Measured by Hamilton Anxiety 14 Item Scale (HAM-A)
Change in HAM-A total score (total score 0-56), calculated as Week 9 value - baseline value, where lower scores indicate less anxiety.
Time frame: Baseline to Week 9
Population: All randomized patients who took at least one dose of study medication and had at least one post baseline assessment, with last observation carried forward to week 9 for patients who did not complete the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change From Baseline in Anxiety Symptoms Measured by Hamilton Anxiety 14 Item Scale (HAM-A) | -11 units on a scale | Standard Deviation 6 |
| Placebo | Change From Baseline in Anxiety Symptoms Measured by Hamilton Anxiety 14 Item Scale (HAM-A) | -5 units on a scale | Standard Deviation 8 |
Secondary
Change From Baseline in Health-related Quality of Life, Enjoyment and Satisfaction (Q-LES-Q)
Q-LES-Q as percent of maximum (0 to 100%) calculated as Week 9 - baseline, where higher values indicate better quality of life.
Time frame: Baseline to Week 9
Population: All randomized patients who took at least one dose of study medication and had at least one post baseline assessment, with last observation carried forward to week 9 for patients who did not complete the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change From Baseline in Health-related Quality of Life, Enjoyment and Satisfaction (Q-LES-Q) | 17 Percentage of Improvement | Standard Deviation 14 |
| Placebo | Change From Baseline in Health-related Quality of Life, Enjoyment and Satisfaction (Q-LES-Q) | 9 Percentage of Improvement | Standard Deviation 14 |
Secondary
Change From Baseline in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index
The Pittsburgh Sleep Quality Index is an eighteen questionnaire scored with 7 sleep component scores each on a 0 to 3 scale, total score range from 0 to 21, worst value 21, best value 0
Time frame: Baseline to Week 9
Population: All randomized patients who took at least one dose of study medication and had at least one post baseline assessment, with last observation carried forward to week 9 for patients who did not complete the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change From Baseline in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index | -6 units on scale | Standard Deviation 4 |
| Placebo | Change From Baseline in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index | -3 units on scale | Standard Deviation 4 |
Secondary
Change From Baseline in Somatic Symptoms Cluster From the Hamilton Anxiety Scale (HAM-A)
The Somatic symptom Cluster of the Hamilton Anxiety Scale is a 7 item cluster associated with somatic symptoms \*somatic muscular, somatic sensory, cardiovascular system, respiratory system, gastrointestinal system, genitourinary system, autonomic system) with a range of values from 0 to 28, worst value 28, best value 0
Time frame: Baseline to Week 9
Population: All randomized patients who took at least one dose of study medication and had at least one post baseline assessment, with last observation carried forward to week 9 for patients who did not complete the study.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change From Baseline in Somatic Symptoms Cluster From the Hamilton Anxiety Scale (HAM-A) | -4 units on scale | Full Range -15.7 |
| Placebo | Change From Baseline in Somatic Symptoms Cluster From the Hamilton Anxiety Scale (HAM-A) | -2 units on scale | Full Range -14.6 |
Secondary
Change From Baseline in Suicidal Thoughts as Measured by Montgomery-Asberg Depression Rating Scale (MADRS) Item 10
The suicide item is a single item of the Montgomery-Asberg Depression Rating Scale with a range of values from 0 to 6, worst value 6, best value 0
Time frame: Baseline to Week 9
Population: All randomized patients who took at least one dose of study medication and had at least one post baseline assessment, with last observation carried forward to week 9 for patients who did not complete the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quetiapine XR | Change From Baseline in Suicidal Thoughts as Measured by Montgomery-Asberg Depression Rating Scale (MADRS) Item 10 | 0 units on scale |
| Placebo | Change From Baseline in Suicidal Thoughts as Measured by Montgomery-Asberg Depression Rating Scale (MADRS) Item 10 | 0 units on scale |
Secondary
Tolerability as Measured by Adverse Event Withdrawals During Treatment
Time frame: Baseline to Week 9
Population: All Randomized patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | Tolerability as Measured by Adverse Event Withdrawals During Treatment | 16 Participants |
| Placebo | Tolerability as Measured by Adverse Event Withdrawals During Treatment | 7 Participants |