Preventing Depression in People Receiving Mechanical Ventilation in an Intensive Care Unit

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.

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