Depression
Conditions
Keywords
Critical Illness, Intensive Care Unit, Acute Respiratory Failure, Prolonged Mechanical Ventilation
Brief summary
This study will determine the effectiveness of antidepressant medication in preventing depression and improving recovery in people who have been supported by mechanical ventilators in an intensive care unit (ICU).
Detailed description
More than one third of all people admitted to ICUs in hospitals require mechanical ventilation for respiratory failure. Many people who survive after being on mechanical ventilation for a prolonged time have significant issues with recovery and quality of life when discharged from the ICU. They are also more prone to depression, which increases patient suffering and the need for medical care, decreases quality of life, and is associated with increased mortality. Previous research indicates that antidepressant medications may improve quality of life and recovery in people who have had a heart attack, but that behavioral treatments are not effective in this case. Treating depression in ICU patients with respiratory failure has not been examined. In this study, antidepressant medications will be given to people who have been on mechanical ventilation in an ICU to determine the effectiveness of antidepressants in improving medical recovery and quality of life. Only a small number of participants will be enrolled in this trial to test the methods and theory; if it is successful, a larger trial will be conducted to determine whether these findings can be widely generalized. Participation in this study will last 8 weeks, with follow-up assessments lasting for 6 months. Participants on a ventilation machine will be randomly assigned to receive either escitalopram, which is an FDA-approved antidepressant, or a placebo pill. A healthy surrogate may need to enroll participants in the study, because participants will begin treatment while in the ICU and may not be able to make an informed decision. The medication or placebo treatment will last for 2 months, continuing at the participant's home after discharge from the ICU. Dosage levels will begin at 10 mg per day and will be increased to 20 mg per day for some participants after 3 to 5 weeks. Every 2 weeks, participants will complete questionnaires by phone or in person about their medical and psychological symptoms and about whether they are taking the study medication. At 8 weeks, participants will complete an in-person interview about depression symptoms, quality of life, and physical function. At 9 weeks, participants will complete a telephone interview about medication withdrawal. Finally, at 4 and 6 months, participants will complete interviews about depression and general health.
Interventions
DRUGEscitalopram
10 mg of escitalopram administered enterally with the option for dose escalation to 20 mg after 3 to 5 weeks if the medical condition is stable and no liver disease presents
DRUGPlacebo
Placebo pills for 8 weeks
Sponsors
National Institute of Mental Health (NIMH)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly mechanically ventilated via an endotracheal tube * Expected to remain intubated for at least 48 hours * Fluent in English or Spanish
Exclusion criteria
* Depression before admission to the ICU, as determined by a proxy interview * Use of antidepressant medication within the last 2 weeks or a monoamine oxidase (MAO) inhibitor in the previous month * History of suicide attempt * Ventricular arrhythmias or a seizure requiring medication in the last 6 months * History of retinal vascular proliferation or bleeding * Migraine headaches treated with 5-HT1 agonists * Organ transplant within the last 6 months * Score of less than 4 on the Glasgow coma scale, in the absence of drug effects, for 2 days * Acute brain hemorrhage * Increased intracranial pressure * Active bleeding or less than 20,000 platelets/ul * Expected prolonged inability to enterally administer escitalopram * Residence more than 75 miles from study facility * Serum sodium less than 125 mEq/l * Hypersensitivity to citalopram or escitalopram * Pregnant, breastfeeding, or possibly becoming pregnant in the next 3 months * Undergoing life-support withdrawal or very low likelihood of 2-month survival * Cognitive or communication impairment severe enough to preclude a conversation with an interviewer present before admission to ICU
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Recruitment Feasibility, Defined as the Number of Participants Recruited and Administered a Medication Dose Within 48 Hours of Mechanical Ventilation | Measured within 2 days of participant recruitment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Will Receive 8 Weeks of Escitalopram Treatment. Participants will receive 8 weeks of escitalopram treatment.
Escitalopram: 10 mg of escitalopram administered enterally with the option for dose escalation to 20 mg after 3 to 5 weeks if the medical condition is stable and no liver disease presents | 7 |
| Participants Will Receive 8 Weeks of Placebo Pills. Participants will receive 8 weeks of placebo pills.
Placebo: Placebo pills for 8 weeks | 8 |
| Total | 15 |
Baseline characteristics
| Characteristic | Participants Will Receive 8 Weeks of Escitalopram Treatment. | Participants Will Receive 8 Weeks of Placebo Pills. | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 8 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 7 participants | 8 participants | 15 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 8 / 8 |
| serious Total, serious adverse events | 0 / 7 | 0 / 8 |
Outcome results
Primary
Recruitment Feasibility, Defined as the Number of Participants Recruited and Administered a Medication Dose Within 48 Hours of Mechanical Ventilation
Time frame: Measured within 2 days of participant recruitment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants Will Receive 8 Weeks of Escitalopram Treatment. | Recruitment Feasibility, Defined as the Number of Participants Recruited and Administered a Medication Dose Within 48 Hours of Mechanical Ventilation | 7 participants |
| Participants Will Receive 8 Weeks of Placebo Pills. | Recruitment Feasibility, Defined as the Number of Participants Recruited and Administered a Medication Dose Within 48 Hours of Mechanical Ventilation | 8 participants |