Improving Sleep and Psychological Functioning in People With Depression and Insomnia

Chronic insomnia is one of the most common symptoms that individuals experience during a
major depressive episode. Insomnia may lead to increased risk for recurrence of major
depression, as well as poor quality of life and increased risk of suicide. Studies have shown
that treating insomnia during a major depressive episode may not only help reduce symptoms of
major depression during the day, but also improve an individual's general quality of life.
Thus, sleeping pills, also known as hypnotics, are commonly prescribed for people with
psychiatric disorders. However, little is known about the safety and efficacy of combining
sleeping pills with antidepressant medications. This study will evaluate the safety and
effectiveness of treatment with both a sleeping pill and antidepressant medication in
improving sleep and psychological functioning in people with depression and insomnia.

Participants in this double-blind study will first receive fluoxetine, an antidepressant
medication, for 1 week. Participants whose symptoms of insomnia subside after this initial
week will continue on fluoxetine for the duration of the study and will not receive sleeping
pills. Those who do not experience an improvement in their symptoms of insomnia after 1 week
will be randomly assigned to receive either placebo or eszopiclone, which is a sleeping pill,
in addition to fluoxetine. All treatments will be given for 8 weeks. Participants will attend
study visits at various points throughout the treatment phase. Follow up visits will occur
periodically over the next 4 months. Assessments will include physiological measures during
sleep, mood, suicidal thinking, quality of life and actigraphy, which measures the amount of
movement during sleep.

Inclusion Criteria:

- Score of greater than 10 on the Primary Care Evaluation of Mental Disorders Patient
Health Questionnaire (PRIME-MD-PHQ) telephone screen

- Diagnosis of major depressive episode based on the Structured Clinical Interview for
DSM-IV (SCID)

- Score of greater than 20 on the Hamilton Rating Scale for Depression

- Meets research diagnostic criteria for insomnia disorder at least 4 nights per week

- Reported mean sleep latency greater than 30 minutes and mean sleep efficiency less
than 85%

- Suitable for outpatient treatment

Exclusion Criteria:

- Use of any psychotropic medications within 2 weeks of initial screening

- Bipolar disorder, schizophrenia, psychotic depression, or any other psychotic disorder

- Uncontrolled asthma or chronic obstructive pulmonary disease

- Chronic pain that may be a significant sleep-disturbing factor

- Uncontrolled thyroid disease

- Poorly controlled diabetes mellitus

- Poorly compensated congestive heart failure

- Currently taking lipophilic beta blockers, opioids, glucocorticoids, theophylline, or
other medications known to interfere with sleep

- History of intolerance or treatment resistance to either fluoxetine or eszopiclone

- Inability to abstain from taking any psychotropics other than the study medications
during the course of the protocol, including sedating antihistamines

- Use of any herbal or naturopathic treatments for sleep or mood (i.e., St. John's wort,
melatonin, kava kava, valerian root, etc.)

- Currently undergoing behavioral, cognitive-behavioral, or interpersonal therapy

- Pregnant or breastfeeding

- Agrees to use an effective form of contraception for the duration of the study

- Uncontrolled symptoms of menopause, including hot flashes

- Uncontrolled hypertension (systolic blood pressure consistently greater than 140 mm
Hg, diastolic blood pressure consistently greater than 90 mm Hg)

- Diagnosis of sleep apnea, periodic limb movement disorder, or restless leg syndrome

- Reports habitual bedtime earlier than 9 PM or later than 1 AM more than 2 times per
week

- Reports habitual rising time later than 9 AM more than 2 times per week

- Body mass index greater than 30

- Consumes more than 3 alcoholic beverages per day

- Consumes more than 4 caffeinated beverages per day

- Habitual smoking between 11 PM and 7 AM

- Use of illicit drugs

- Score greater than 24 on the Mini Mental State Examination

- Determined to be incompetent

- Determined to be at imminent risk for suicide

- More than 5 lifetime SCID diagnoses of major depressive episodes

- More than 3 failed antidepressant trials during the current episode of depression, as
determined by the Antidepressant Treatment History Form

- A course of electroconvulsive therapy during the present depressive episode