The Quietude Study: Quetiapine Use for Agitated Depression

Sponsor

Physicians Research And Education Network (Other)

Overall Status

Terminated

CT.gov ID

NCT01363310

Collaborator

(none)

250

Enrollment

Locations

Arms

28.1

Duration (Months)

22.7

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression With Prominent Agitation	Drug: Quetiapine XR Drug: Escitalopram	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Jan 1, 2013

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Quetiapine XR	Drug: Quetiapine XR Dosage form: tablets Day 1-2: 50 mg Day 3-7: 150 mg Day 8-57: either 150 or 300 mg/day (flexible) Other Names: Seroquel XR
Active Comparator: Escitalopram	Drug: Escitalopram Dosage form: capsules Day 1-7: 10 mg Day 8-57: 10 or 20 mg/day (flexible)

Arm

Intervention/Treatment

Active Comparator: Quetiapine XR

Drug: Quetiapine XR

Dosage form: tablets Day 1-2: 50 mg Day 3-7: 150 mg Day 8-57: either 150 or 300 mg/day (flexible)

Other Names:

Seroquel XR

Active Comparator: Escitalopram

Drug: Escitalopram

Dosage form: capsules Day 1-7: 10 mg Day 8-57: 10 or 20 mg/day (flexible)

Outcome Measures

Primary Outcome Measures

Change from baseline to endpoint in the Hamilton Depression Rating Scale 17-Item (HAMD-17) total score [Day 1, Day 57]
A tool to assess the range of symptoms of depression

Secondary Outcome Measures

Change in anxiety factor score on the Hamilton Depression Rating Scale 17-item (HAMD-17) from baseline to endpoint [Day 1, Day 57]
A tool to assess the range of symptoms of depression
Change from baseline to endpoint in Hamilton Anxiety Rating Scale (HAMA) total score [Day 1, Day 57]
A tool to measure severity of symptoms of anxiety
Change in Clinical Global Impression score from baseline to endpoint [Screening Visit, Day 1, Day 8, Day 15, Day 29, Day 43, Day 57]
A tool to assess illness severity, improvement and response to treatment
Change from baseline to endpoint in Sheehan Disability Scale (SDS) sub-scales and total score [Day 1, Day 57]
A tool to assess functional impairment
Change in Hamilton Depression Rating Scale 17-item (HAMD-17) sleep disturbance factor score on the from baseline to endpoint [Day 1, Day 57]
A tool to assess the range of symptoms of depression
Change in Hamilton Anxiety Rating Scale (HAMA) somatic and psychic anxiety factor scores from baseline to endpoint [Day 1, Day 57]
A tool to measure severity of symptoms of anxiety
Change from baseline in the Sex Functioning Questionnaire (Sex FX) [Day 1, Day 57]
A tool to assess sexual functioning
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Known lack of antidepressant response to escitalopram at a dose of at least 10 mg/day
Known intolerance or hypersensitivity to quetiapine or escitalopram
Treatment with Electroconvulsive therapy within 90 days prior to baseline
Use of Potent P450 3A4 inhibitors or inducers within 14 days of baseline
AST & ALT ≥ 3X ULN
TSH ≥ 10% ULN
Unstable medical condition
Medical condition the would affect absorption, distribution, metabolism or excretion of study treatment
Significant ECG abnormalities
Pregnancy or lactation
Patients with increased suicidal risks, HAM-D item 3 ≥3 or have made a suicide attempt within the past 6 months.
Patients who, in the investigators opinion, will require psychotherapy (other than supportive psychotherapy) during the study period, unless psychotherapy has been ongoing for a minimum of 3 months prior to randomisation
A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
Unstable DM defined as enrolment glycosylated haemoglobin (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 randomisation. 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 Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study
Clinically significant deviation from the reference range in clinical laboratory test results
An absolute neutrophil count (ANC) of 1.5 x 109 per liter
Those who are involved in the planning and/or conduct of the study cannot be enrolled as subjects
Previous enrolment or randomization in the present study
Participation in another medication trial within 4 weeks prior to enrolment into the study herein

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aggarwal and Associates Ltd	Brampton	Ontario	Canada	L6T 0G1
2	Aptekar Medicine Professional Corporation	Brampton	Ontario	Canada	L6W 2A4
3	Chatham-Kent Health Alliance	Chatham	Ontario	Canada	N7L 1B7
4	Fort Erie Group Family Practice	Fort Erie	Ontario	Canada	L2A 1Z3
5	Georgina Family Medical Centre	Keswick	Ontario	Canada	L4P 2C7
6	Richmond Oxford Walk-In Clinic	London	Ontario	Canada	N6A 5G6
7	Gerald Rockman Medicine Professional Corporation	Scarborough	Ontario	Canada	M1N 1W8
8	Brady Clinic	Sudbury	Ontario	Canada	P3E 1H5
9	Bloor-Park Medical Centre	Toronto	Ontario	Canada	M6G 1L4
10	Primary Care Lung	Toronto	Ontario	Canada	M6H 3M2
11	Manna Research	Toronto	Ontario	Canada	M9W 4L6