A Multi-Centre, Double-Blind, Randomised, Parallel Group, Escitalopram Controlled Phase III-B Study of the Efficacy and Safety of Quetiapine Fumarate Extended Release (Seroquel XR TM) as Monotherapy in the Treatment of Adult Patients With Agitated Major Depressive Disorder
Overview
- Phase
- Phase 3
- Intervention
- Quetiapine XR
- Conditions
- Depression With Prominent Agitation
- Sponsor
- Physicians Research And Education Network
- Enrollment
- 250
- Locations
- 11
- Primary Endpoint
- Change from baseline to endpoint in the Hamilton Depression Rating Scale 17-Item (HAMD-17) total score
- Status
- Terminated
- Last Updated
- 12 years ago
Overview
Brief Summary
Most individuals with major depressive disorder manifest clinically significant agitation. Concurrent agitation in a depressed individual is associated with an intensification of mood symptoms, decreased probability of recovery, increased recurrence risk, suicidality, and increased medical-service utilization. The occurrence of anxiety/agitation phenomenology in the depressed patient often invites the need for augmentation strategies (e.g. atypical antipsychotics, benzodiazepines, etc.) and complicated polypharmacy regimens. Moreover, individuals with major depressive disorder often report worsening of symptom severity, irritability, hostility, dysphoria, and significant subjective distress (This response pattern is similar to individuals with bipolar disorder).
Results from large research studies provide evidence indicating that quetiapine is capable of offering clinically significant multidimensional symptom relief in bipolar depression. Moreover, results from several trials in major depressive disorder and generalized anxiety disorder have established the efficacy of quetiapine therapy for unipolar depression and anxiety syndromes. So far, no atypical antipsychotic agent has been evaluated specifically for the treatment of agitated depression.
In this study, it is hypothesized that persons with major depressive disorder and prominent agitation (i.e. agitated depression) will exhibit a more favourable response and tolerability profile to quetiapine XR when compared to escitalopram.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female
- •Age 18 to 65
- •Outpatient at enrolment
- •A diagnosis of major depressive disorder
- •Baseline HAMD-17 score \> 20 and HAMD Item1 score \> 2 both at enrolment and baseline
- •Significant agitation
- •CGI-S score \> 4 at screening and baseline
- •Negative serum pregnancy test at enrolment and use of a reliable method of birth control during the study
- •Able to understand and comply with the requirements of the study
- •Able and willing to give meaningful informed written consent
Exclusion Criteria
- •Another Axis I diagnosis of primary focus within 6 months of enrolment
- •Axis II disorder causing impact on current diagnosis
- •Current depressive episode \<4 weeks, or \>12 months
- •Substance or alcohol abuse or dependency as defined by DSM IV within 6 months of enrolment
- •Any pervasive developmental disorder or dementing disorder
- •Treatment with other antipsychotics, mood stabilizer or other psychoactive drugs less than 7 days prior to randomization
- •Treatment with fluoxetine less than 28 days prior to baseline
- •Treatment with MAO inhibitors, anxiolytic drugs in excess of 2 mg lorazepam equivalents/day.
- •Insufficient response to more than two antidepressants during the index episode prior to study involvement
- •Known lack of antidepressant response to quetiapine at a dose of at least 50 mg/day x 4 weeks
Arms & Interventions
Quetiapine XR
Intervention: Quetiapine XR
Escitalopram
Intervention: Escitalopram
Outcomes
Primary Outcomes
Change from baseline to endpoint in the Hamilton Depression Rating Scale 17-Item (HAMD-17) total score
Time Frame: Day 1, Day 57
A tool to assess the range of symptoms of depression
Secondary Outcomes
- Change in anxiety factor score on the Hamilton Depression Rating Scale 17-item (HAMD-17) from baseline to endpoint(Day 1, Day 57)
- Change from baseline to endpoint in Hamilton Anxiety Rating Scale (HAMA) total score(Day 1, Day 57)
- Change in Clinical Global Impression score from baseline to endpoint(Screening Visit, Day 1, Day 8, Day 15, Day 29, Day 43, Day 57)
- Change from baseline to endpoint in Sheehan Disability Scale (SDS) sub-scales and total score(Day 1, Day 57)
- Change in Hamilton Depression Rating Scale 17-item (HAMD-17) sleep disturbance factor score on the from baseline to endpoint(Day 1, Day 57)
- Change in Hamilton Anxiety Rating Scale (HAMA) somatic and psychic anxiety factor scores from baseline to endpoint(Day 1, Day 57)
- Change from baseline in the Sex Functioning Questionnaire (Sex FX)(Day 1, Day 57)
- Change in blood pressure and heart rate from baseline to end of treatment(Day 1, Day 57)
- Change in weight, BMI, waist circumference from baseline to end of treatment(Day 1, Day 57)
- Change in findings from physical examination from baseline to end of treatment(Screening, Day 57)
- Tabulation of spontaneous adverse events(Day 1, Day 57)
- Tabulation of clinical haematology and chemistry results(Screening, Day 57)
- Incidence of premature study withdrawal due to inadequate control of depressive symptoms
- Proportion of patients with HAM-D Item 3 score > 2 at any time after randomization or adverse events of suicidality/suicidal ideation/suicide attempts/suicide completion(Day 1, Day 57)