Improving Sleep and Psychological Functioning in People With Depression and Insomnia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Hypnotics in the Treatment of Psychiatric Disorders

Conditions
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Sleep Initiation and Maintenance Disorders, Depression

Intervention / Treatment
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* Drug: Eszopiclone
* Drug: Fluoxetine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Participants will receive treatment with eszopiclone and fluoxetine | Drug: Eszopiclone<br>* Eszopiclone 3 mg every night for 8 weeks<br>Drug: Fluoxetine<br>* Fluoxetine 20 mg every morning for 9 weeks<br>|
| Active Comparator: B<br>Participants will receive treatment with placebo and fluoxetine | Drug: Fluoxetine<br>* Fluoxetine 20 mg every morning for 9 weeks<br>Drug: Placebo<br>* Placebo every night for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Living and Role Functioning (DLRF) Basis-32 Subscale Ratings | The BASIS 32 psychometric includes several subscales, including daily living and role functioning (DLRF). These subscales are rated from 0-4, with higher scores indicating a greater deal of difficulty in this dimension and lower scores denoting better outcomes. Measured weekly for 9 weeks. Reported as mean of 9 weeks. | 9 weeks | 
| Relation to Self/Others (RSO) Basis-32 Subscale Ratings | The BASIS 32 psychometric includes several subscales, including relation to self and others (RSO). These subscales are rated from 0-4, with higher scores indicating a greater deal of difficulty in this dimension. Measured weekly for 9 weeks. Reported as mean of 9 weeks. | 9 weeks | 
| Quality of Life Ratings, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | The Q-LES-Q is scored from 0-100, with higher scores better than lower. Measured weekly for 9 weeks. Reported as mean of 9 weeks. | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insomnia Severity Index (ISI) | The Insomnia Severity Index has seven questions. The seven answers are added up to get a total score, range 0-28. Lower scores represent better outcomes. Total score categories: 0-7 = No clinically significant insomnia, 8-14 = Subthreshold insomnia, 15-21 = Clinical insomnia (moderate severity), 22-28 = Clinical insomnia (severe). | 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Hypnotics, Sleep, Quality of Life, Insomnia, Suicide