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

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 Overview

• Status: Completed
• Conditions: Severe Asthma; Moderate or Severe Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Escitalopram

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • The UT Southwestern Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo Matching Escitalopram given orally daily (for a 12-week duration).	Drug: Placebo; Placebo Matching Escitalopram; Other Names: Placebo Matching Escitalopram
Active Comparator: Escitalopram; 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.	Drug: Escitalopram; Active Escitalopram

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HAM-D (Hamilton Rating Scale for Depression)	The HAM-D is a 17 item questionnaire (a clinician-administered depression scale) designed to evaluate severity of depressive symptoms. Scores can range from 0 to 52. The higher the score, the worse the depressive symptoms (worse outcome).	Baseline
ACQ (Asthma Control Questionnaire)	The ACQ is a questionnaire used to assess symptoms pertinent to asthma management. Scores range from 0 to 42. The higher the score, the worse the asthma symptoms (worse outcome). The total ACQ score is obtained by dividing the raw score by the total number of items (in this case 7 items).	Baseline
IDS-SR (Inventory of Depressive Symptomatology - Self-Report)	The IDS-SR is a 30 item (self-report questionnaire) designed to assess symptoms of depression. Scores range from 0 to 90. The higher the score, the worse the depressive symptoms (worse outcome).	Baseline
HAM-D (Hamilton Rating Scale for Depression)	The HAM-D is a 17 item questionnaire (a clinician-administered depression scale) designed to evaluate severity of depressive symptoms. Scores can range from 0 to 52. The higher the score, the worse the depressive symptoms (worse outcome).	Up to 12 weeks
ACQ (Asthma Control Questionnaire)	The ACQ is a questionnaire used to assess symptoms pertinent to asthma management.Scores range from 0 to 42. The higher the score, the worse the asthma symptoms (worse outcome). The total ACQ score is obtained by dividing the raw score by the total number of items (in this case 7 items).	Up to 12 weeks
IDS-SR (Inventory of Depressive Symptomatology - Self-Report)	The IDS-SR is a 30 item (self-report questionnaire) designed to assess symptoms of depression. Scores range from 0 to 90. The higher the score, the worse the depressive symptoms (worse outcome).	Up to 12 weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: E. Sherwood Brown, Ph.D, M.D., UT Southwestern Medical Center at Dallas

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: February 11, 2008
• First Submitted That Met QC Criteria: February 21, 2008
• First Posted (Estimate): February 22, 2008

Study Record Updates

• Last Update Posted (Estimate): February 4, 2014
• Last Update Submitted That Met QC Criteria: January 2, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Depression; Asthma; Escitalopram
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Respiratory Tract Diseases; Mood Disorders; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Depression; Depressive Disorder; Asthma; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide
• Other Study ID Numbers: 092007-057