The Quietude Study: Quetiapine Use for Agitated Depression

Physicians Research And Education Network

Status and phase

Terminated

Phase 3

Conditions

Depression With Prominent Agitation

Treatments

Drug: Quetiapine XR

Drug: Escitalopram

Study type

Interventional

Funder types

Other

Identifiers

NCT01363310

D1443C00037

Details and patient eligibility

About

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.

Enrollment

250 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No 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