Depression, Sleep Initiation and Maintenance Disorders
Conditions
Keywords
Depression, Hypnotics, Sleep, Quality of Life, Insomnia, Suicide
Brief summary
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
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.
Interventions
DRUGEszopiclone
Eszopiclone 3 mg every night for 8 weeks
DRUGFluoxetine
Fluoxetine 20 mg every morning for 9 weeks
DRUGPlacebo
Placebo every night for 8 weeks
Sponsors
National Institute of Mental Health (NIMH)
Sumitomo Pharma America, Inc.
Philips Healthcare
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Living and Role Functioning (DLRF) Basis-32 Subscale Ratings | 9 weeks | 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. |
| Relation to Self/Others (RSO) Basis-32 Subscale Ratings | 9 weeks | 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. |
| Quality of Life Ratings, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | 9 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insomnia Severity Index (ISI) | 9 weeks | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine (FLX) Plus Eszopiclone (ESZ) Participants will receive treatment with eszopiclone and fluoxetine | 30 |
| FLX Plus Placebo Participants will receive treatment with placebo and fluoxetine | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | FLX Plus Placebo | Fluoxetine (FLX) Plus Eszopiclone (ESZ) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 30 Participants | 60 Participants |
| Age, Continuous | 38.0 years STANDARD_DEVIATION 12.5 | 44.9 years STANDARD_DEVIATION 11.7 | 41.5 years STANDARD_DEVIATION 12.5 |
| BASIS 32 DLRF | 2.0 units STANDARD_DEVIATION 0.7 | 1.9 units STANDARD_DEVIATION 0.7 | 2.0 units STANDARD_DEVIATION 0.7 |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 40 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
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.
Time frame: 9 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine (FLX) Plus Eszopiclone (ESZ) | Daily Living and Role Functioning (DLRF) Basis-32 Subscale Ratings | 0.81 units on a scale | Standard Deviation 0.64 |
| FLX Plus Placebo | Daily Living and Role Functioning (DLRF) Basis-32 Subscale Ratings | 1.2 units on a scale | Standard Deviation 0.72 |
Primary
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.
Time frame: 9 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine (FLX) Plus Eszopiclone (ESZ) | Quality of Life Ratings, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | 50.2 units on a scale | Standard Deviation 8.11 |
| FLX Plus Placebo | Quality of Life Ratings, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | 46.9 units on a scale | Standard Deviation 9 |
Primary
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.
Time frame: 9 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine (FLX) Plus Eszopiclone (ESZ) | Relation to Self/Others (RSO) Basis-32 Subscale Ratings | 0.74 units on a scale | Standard Deviation 0.71 |
| FLX Plus Placebo | Relation to Self/Others (RSO) Basis-32 Subscale Ratings | 1.04 units on a scale | Standard Deviation 0.77 |
Secondary
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).
Time frame: 9 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine (FLX) Plus Eszopiclone (ESZ) | Insomnia Severity Index (ISI) | 21.1 units on a scale | Standard Deviation 4 |
| FLX Plus Placebo | Insomnia Severity Index (ISI) | 20.2 units on a scale | Standard Deviation 4.1 |