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

• Proportion of planned study doses actually administered to participants [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Proportion of completed interviews, excluding follow-ups [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Participant reconsent rate [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Proportion of participants enrolled compared to all eligible participants [ Time Frame: Measured 1 day after recruitment ] [ Designated as safety issue: No ]
• Rate, timing, and tolerability of medication dose escalation to 20 mg [ Time Frame: Measured after 5 weeks ] [ Designated as safety issue: Yes ]
• Rate of off-protocol antidepressant use [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: Yes ]
• Success of experimental medication blinding [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Depression severity, measured by Center for Epidemiological Studies Depression Scale (CES-D), between the two arms [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Depression severity, measured by the 17-item Hamilton Depression Scale (HAM-D17) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Depression severity, measured by Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Rate of suicide attempts and suicidal ideation [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: Yes ]
• Rate and severity of medication withdrawal symptoms [ Time Frame: Measured after 9 weeks ] [ Designated as safety issue: Yes ]
• Proportion of major depressive episodes and incidences of major depressive disorder, measured by the Structured Clinical Interview for DSM-IV (SCID) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Quality of life, measured by the 12-item Short Form Health Survey (SF-12) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Rates of adverse events, serious adverse events, and deaths after the end of treatment [ Time Frame: Measured after 12 weeks ] [ Designated as safety issue: Yes ]
• Participant burden, defined as the time taken for completion of the study questionnaires [ Time Frame: Measured after 12 weeks ] [ Designated as safety issue: No ]

• Proportion of planned study doses actually administered to participants [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Proportion of completed interviews, excluding follow-ups [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Participant re-consent rate [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Proportion of participants enrolled compared to all eligible participants [ Time Frame: Measured 1 day after recruitment ] [ Designated as safety issue: No ]
• Rate, timing, and tolerability of medication dose escalation to 20 mg [ Time Frame: Measured after 5 weeks ] [ Designated as safety issue: Yes ]
• Rate of off-protocol antidepressant use [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: Yes ]
• Success of experimental medication blinding [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Depression severity, measured by Center for Epidemiological Studies Depression Scale (CES-D), between the two arms [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Depression severity, measured by the 17-item Hamilton Depression Scale (HAM-D17) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Depression severity, measured by Montgomery Åsberg Depression Rating Scale (MADRS) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Rate of suicide attempts and suicidal ideation [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: Yes ]
• Rate and severity of medication withdrawal symptoms [ Time Frame: Measured after 9 weeks ] [ Designated as safety issue: Yes ]
• Proportion of major depressive episodes and incidences of major depressive disorder, measured by the Structured Clinical Interview for DSM-IV (SCID) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Quality of life, measured by the 12-item Short Form Health Survey (SF-12) [ Time Frame: Measured after 8 weeks ] [ Designated as safety issue: No ]
• Rates of adverse events, serious adverse events, and deaths after the end of treatment [ Time Frame: Measured after 12 weeks ] [ Designated as safety issue: Yes ]
• Participant burden, defined as the time taken for completion of the study questionnaires [ Time Frame: Measured after 12 weeks ] [ Designated as safety issue: No ]

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).

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.

• Drug: 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
  Other Name: Lexapro
• Drug: Placebo
  Placebo pills for 8 weeks

• Experimental: 1
  Participants will receive 8 weeks of escitalopram treatment.
  Intervention: Drug: Escitalopram
• Placebo Comparator: 2
  Participants will receive 8 weeks of placebo pills.
  Intervention: Drug: Placebo

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