A 12-week, randomized, double-blind, parallel-group, placebo-controlled acute phase trial of escitalopram is proposed in 222 persons with asthma and Major Depressive Disorder (MDD). This sample will consist of 80 stratified into the High severity group which will consist of a baseline score \> or = 20 on the 17-item Hamilton Rating Scale for Depression (HRSD) and \> or = 3 courses of oral corticosteroids in the past 12 months. A separate group stratified into the Low severity group of 142 with MDD and asthma but HRSD-17 scores of \< 20 and \< 3 courses of oral corticosteroids in the past 12 months. A 16 week continuation phase is also proposed for depression responders at week 12. The participants will be recruited at the Parkland Hospital Health System (PHHS) Asthma and Allergy Clinics and Aston Clinic using the Self-Report Screening Tool for Depression (2-SRSD), a brief depression questionnaire, as part of routine clinical practice. Potential participants will be given an appointment scheduled at the PI's office to complete baseline assessment at which time written informed consent will be obtained before any study-specific assessments are completed. At the baseline appointment, the RA will administer the Structured Clinical Interview for DSM-IV (SCID) at baseline to establish a current diagnosis of MDD. Participants meeting all inclusion criteria will then be administered the IDS-SR30, the SF-36, the Asthma Control Questionnaire (ACQ), Mini Asthma Quality of Life Questionnaire (Mini AQLQ), the Cumulative Illness Rating Scale (CIRS), the PRD-III Somatic Symptom Scale (PRD-III) for side effects, a blood draw for routine laboratory analyses, and forced expiratory volume in 1-second percentage of normal (FEV1%) will be assessed using a portable spirometer. Self-reported asthma-related emergency room visits and hospitalizations will be quantified for the past 12 months.

Participants will receive a clinical psychiatric evaluation by one of the investigators to confirm the diagnosis and that the participant meets entry criteria. Steroid inhaler dose monitoring using the counter already included by the manufacturer will begin at this time. After the participant is determined to qualify, the steroid inhaler counter will be used to assess baseline adherence. Participants will be randomized and receive either escitalopram or a placebo identical in appearance. Each participant will then be given a 14-day supply of active medication (escitalopram 10 mg) or placebo and asked to return for a follow-up appointment in two weeks. Each participant will be given a phone number to reach the Principle Investigator (PI) and Research Assistant (RA) 24 hours a day. The RA will obtain written consent to inform the physician treating their asthma of their participation in the study. Each participant will then return for follow-up appointments twice per month at which time they will repeat the outcome measures according to the schedule given below. Pill counts will be conducted, MEMS caps analyzed and a list of current medications and doses will be obtained at each visit. Participants will be evaluated by both the RA and PI at each follow-up appointment. Participants who have not shown evidence of adequate response (\< 30% decrease in HRSD) to the antidepressant at week 4, and who do not have side effects, will have the dose increased to two tablets (20 mg of active medication or placebo). At week 12, responders (HRSD reduction ≥50% from baseline) will continue on blinded treatment with assessments every 4 weeks for an additional 16 weeks (continuation phase). Nonresponders will be removed from the study and given standard treatment by an unblinded psychiatrist (Dr. Nakamura) until referral can be made for further treatment. Continuation phase will begin at the final week 12 assessment for responders. They will be given a 4-week supply of medication at the dose they are taking at week 12, and instructions to call if they experience a worsening in symptoms (e.g., decrease in sleep, suicidal thoughts) between the 4-week appointments, and an appointment with a study physician will be arranged. The HRSD will be assessed at any interim appointments and the participant discontinued if they meet discontinuation criteria. Treatment referral will be arranged as in the acute phase study. At completion of 28 weeks, they will be referred for further treatment as appropriate, with their PCP, the Parkland Psychiatry Clinic, a private psychiatrist, a UT Southwestern Medical Center, or the county Mental Health Mental Retardation (MHMR) system. Parking/bus tokens will be provided. A final visit for safety, to assess follow-up adherence and collect asthma and depression outcome data will be arranged 4 weeks after the last appointment (e.g., discontinuation at end of acute phase, end of continuation phase, or if discontinued early for any reason).

The assessment schedule is designed to approximate good clinical practice for depression and, thus, may be somewhat less intensive than in some antidepressant trials. The following assessment instruments will be used in this investigation. A two-item, self-report screening tool for depression (2-SRSD) taken from the Primary Care Evaluation of Mental Disorders Procedure (PRIME-MD) screening interview will be used to detect suspected cases of depression among asthma clinic patients. The specificity of the 2-SRSD in this population was 57%. Thus, we expect to identify almost all true positives, with a substantial number of false positives. A positive answer to either 1) "During the past month, have you often been bothered by feeling down, depressed, or hopeless?" or 2) "During the past month, have you often been bothered by little interest or pleasure in doing things?" will be considered a possible case of depression and qualify for further assessment. MDD is defined as at least five of nine symptoms that must include depressed mood or loss of interest and can also include psychomotor changes, appetite changes or weight loss, sleep changes, decreased concentration, guilt, decreased energy levels (lassitude), and suicidal ideation. The symptoms must occur at the same time and last for at least 2 weeks and be associated with a change in functioning. The symptoms must not be the direct physiologic effect of a drug or medical illness (e.g., hypothyroidism) or bereavement. MDD is diagnosed using a structured clinical interview that addresses each symptom and uses information from the patient, family, physicians, and medical records to establish the diagnosis.

The clinician version of the structured Clinical Interview for DSM-IV (SCID) is a brief structured interview for major Axis I disorders in DSM-IV including major depressive disorder, dysthymic disorder, bipolar disorders, psychotic disorders, anxiety disorders, eating disorders, and alcohol and substance abuse/dependence. The Hamilton Rating Scale for Depression (HRSD, 17-item version) is an observer-rated measure of depressive symptomatology. The HRSD will be administered at every visit. The Inventory of Depressive Symptomatology-Self-report (IDS-SR30) is a 30-item self-report scale that assesses depressive symptom severity. The IDS-SR30 will be administered at every visit. The Hamilton Rating Scale for Anxiety (HRSA) is a 14-item observer rating scale that assesses the degree and pathology associated with anxiety such as anxious mood, tension, fear, and insomnia. The HRSA will be administered at every visit. Asthma symptoms will be assessed at every visit using the Asthma Control Questionnaire (ACQ). Pulmonary function will also be assessed at every visit by spirometry, using equipment meeting the standards of the ATS, and calibrated according to the manufacturer's recommendations. Spirometry will be performed according to ATS guidelines, as the best of three acceptable efforts. Spirometry will be measured before, and 10 minutes after, two puffs of albuterol are administered via metered dose inhaler. Bronchodilator response is calculated as \[(post FEV1 - pre FEV1)/pre FEV1\], and converted to a percent improvement.

The Psychobiology of Recovery in Depression-III Somatic Symptom Scale (PRD-III) is a 24 item, side effects scale developed for a longitudinal depression study. The PRD-III covers a wide range of common medication side effects and can be quickly and easily administered by a clinician. The PRD-III will be administered at every visit. Asthma-related quality of life will be assessed with the Mini-AQLQ, a 15 item, self-administered scale measuring functional impairments troublesome to adult asthma patients. Mini-AQLQ showed good responsiveness, reliability, and construct validity compared to the longer 32 item version. Both versions of the Mini-AQLQ correlate well with SF 36 mental and physical subscales and ACQ scores (asthma symptoms), but not with spirometry or beta-agonist use. The Mini-AQLQ will be administered at baseline, week 4, week 8, week 12, and at exit or if continued, week 28. General functioning will be assessed with the 36-Item Short Form Health Survey (SF-36), a self-reported tool used to assess physical and mental functioning. The scale consists of summary measures of physical and mental health that can be further divided into scales for physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores above the normative score of 50±10 indicate better than average functioning while scores below 50 suggest below normal functioning. The SF-36 will be administered at baseline, week 4, week 8, week 12, and at exit or if continued, week 28.

Medical illness burden will be assessed at baseline and at exit with the Cumulative Illness Rating Scale (CIRS), a valid and widely used 13-item, 0-4, clinician-rated scale that assesses medical impairment related to major organ systems. Medical history and review of systems is used for the rating. The scale will be rated by a study physician. The scale has been used in other recent antidepressant trials to assess medical illness burden. The Perceived Stress Scale (PSS-10) is a 10-item, 0-4 self-report scale that assesses stressful feelings and thoughts in the past month. The PSS-10 has adequate reliability and validity and is a better predictor of some outcomes (e.g. depressive and physical symptoms, utilization of health services, social anxiety) than were life-event scores. The PSS-10 appears to provide a general appraisal of life stress. The PSS-10 will be administered at baseline, week 4, week 8, week 12, and at exit or if continued, week 28.

Specific Primary and Secondary Outcome Measures associated with primary and secondary aims include:

Primary Aim:

1. Escitalopram treatment will be associated with greater improvement in asthma symptoms, using ACQ measure, than placebo in outpatients with asthma and MDD.

Secondary Aim:

1. Escitalopram treatment will be associated with greater depressive symptom remission rates, using HRSD, than placebo in outpatients with asthma and MDD.