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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Lexapro (Escitalopram)

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 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 Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Texas Southwestern Medical Center

Overall Clinical Trial Officials and Contacts

E. Sherwood Brown, Ph.D, M.D. Principal Investigator UT Southwestern Medical Center at Dallas  

Overall Contact: Daren Denniston, B.S. 214-645-6963 daren.denniston@utsouthwestern.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00621946

Study ID Number: 092007-057

ClinicalTrials.gov Identifier: NCT00621946

Health Authority: United States: Institutional Review Board