Treatment of Outpatients With Severe Asthma and Moderate or Severe Major Depressive Disorder

Escitalopram in the Treatment of Outpatients With Severe Asthma and Moderate or Severe Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

Sponsors

Lead Sponsor: University of Texas Southwestern Medical Center

Collaborator: Forest Laboratories

Source University of Texas Southwestern Medical Center
Brief Summary

The purpose is to determine if: 1) Escitalopram treatment will be associated with less oral corticosteroid use than placebo in outpatients with severe asthma and moderate or severe major depressive disorder (MDD). 2) Escitalopram treatment will be associated with greater improvement in asthma symptoms than placebo in outpatients with severe asthma and moderate or severe MDD. 3) Escitalopram treatment will be associated with greater depressive symptom remission rates than placebo in outpatients with severe asthma and moderate or severe MDD.

Detailed Description

Primary Aim

1) Determine if escitalopram treatment is associated with less oral corticosteroid use for asthma symptom control than placebo in asthma outpatients with moderate or MDD.

Secondary Aims

1. Determine if escitalopram treatment is associated with greater improvement in asthma symptoms than placebo in outpatients with severe asthma and moderate or severe MDD.

2. Determine if escitalopram treatment is associated with greater depressive symptom remission rates than placebo in outpatients with severe asthma and moderate or severe MDD.

Background/Significance

Asthma is a common, chronic general medical condition characterized by inflammation and variable, but usually reversible, airflow obstruction. Approximately 7.2% of people in the United States have a history of asthma. Asthma is common with an increasing prevalence and mortality especially in low-income and minority populations.

The course of asthma appears to be influenced by mood and emotions. It has been reported that there is a high prevalence of depression or depressive symptoms in both children and adults with asthma.

Depression is associated with increased use of asthma-related urgent care services, as well as a variety of unfavorable asthma outcomes. In addition to the possible associations between depression and asthma medication nonadherence and even death, depression appears to be associated with increased use of emergency rooms, hospitals, and unscheduled appointments for asthma.

Despite data on the frequency of depression in asthma and its adverse consequences, it is generally not recognized or treated.

Our proposed study is different. We observed a modest difference between antidepressant and placebo in a prior trial. However, in a subgroup with more severe asthma (based on frequent corticosteroid use) and more severe depression (based on higher depressive symptoms scores) we saw a much larger effect size. The proposed study will target this subgroup. The sample size is based on the effect size we observed in this subgroup in our previous pilot study.

A placebo controlled trial is needed because 1) the primary outcome in our previous trial was not significant. Therefore, it is not clear that antidepressant treatment is effective in depressed asthma patients. 2) We identified a subgroup with greater depressive symptom and asthma severity that based on a post-hoc analysis appeared to show a favorable response to the antidepressant. Thus, we want to confirm these post-hoc findings with a targeted prospective study. In the clinical population we will study, very few patients have ever received assessment or treatment for depression. Therefore, we would not be withholding clearly effective treatment that they would otherwise receive.

Standard of care for severe asthma is aggressive asthma treatment. Our study does not require any changes in the patient's asthma treatment. No guidelines are currently available on the treatment of depression in asthma patients. Standard care for depression would be antidepressants.

Overall Status Completed
Start Date March 2008
Completion Date March 2010
Primary Completion Date March 2010
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
HAM-D (Hamilton Rating Scale for Depression) Baseline
ACQ (Asthma Control Questionnaire) Baseline
IDS-SR (Inventory of Depressive Symptomatology - Self-Report) Baseline
HAM-D (Hamilton Rating Scale for Depression) Up to 12 weeks
ACQ (Asthma Control Questionnaire) Up to 12 weeks
IDS-SR (Inventory of Depressive Symptomatology - Self-Report) Up to 12 weeks
Enrollment 26
Condition
Intervention

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo Matching Escitalopram

Arm Group Label: Placebo

Other Name: Placebo Matching Escitalopram

Intervention Type: Drug

Intervention Name: Escitalopram

Description: Active Escitalopram

Arm Group Label: Escitalopram

Eligibility

Criteria:

Inclusion Criteria:

- Current HAM-D score of ≥ 20

- Patients with severe asthma (defined as asthma requiring three or more course of oral corticosteroids in the past year).

- No changes in asthma medications, oral corticosteroid use, or treatment for respiratory tract infections in the past week

- Needs to have taken ≥ 3 courses of oral corticosteroids, for asthma, in the past 12 months.

- Both male and female

- English- or Spanish-speaking

Exclusion Criteria:

- Current substance or alcohol abuse/dependence

- MDD with psychotic features (delusions, hallucinations, disorganized thought processes)

- Bipolar disorder

- Schizophrenia or schizoaffective disorder

- Substance-induced mood disorder and mood disorder secondary to a general medical condition

- Mental retardation or other severe cognitive impairment

- Prison or jail inmates

- Pregnant or nursing women or women of childbearing age who will not use The University of Texas Southwestern Medical Center - Institutional Review Board (UTSW IRB) approved methods of birth control or abstinence during the study

- Treatment-resistant depressed persons defined as having failed two adequate trials of antidepressants

- Current antipsychotic or antidepressant therapy or psychotherapy

- Initiation of other psychotropic medications or psychotherapy within past 2 weeks (e.g., anxiolytics, hypnotics)

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
E. Sherwood Brown, Ph.D, M.D. Principal Investigator UT Southwestern Medical Center at Dallas
Location
Facility: The UT Southwestern Medical Center at Dallas
Location Countries

United States

Verification Date

January 2014

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Texas Southwestern Medical Center

Investigator Full Name: Sherwood Brown

Investigator Title: Principal Investigator, MD/PhD

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Placebo

Type: Placebo Comparator

Description: Placebo Matching Escitalopram given orally daily (for a 12-week duration).

Label: Escitalopram

Type: Active Comparator

Description: Once daily oral administration (for a 12-week duration) of 10 mg escitalopram tablets with an increase to 20 mg in those with a less than 30% decrease in HAM-D scores at week 4.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov