Depression
Conditions
Keywords
depression, sleep, treatment
Brief summary
The purpose of the study is to determine whether changing sleep patterns improves response to an antidepressant medication.
Detailed description
Depression is common and associated with social and economic costs. Although antidepressant medications are an effective treatment for depression, it can take as long as 6-8 weeks before symptoms improve, and 20-35% of individuals who use antidepressants still experience depression symptoms. New treatments that accelerate response to antidepressants are important to reduce the burden of depression. The objectives of the proposed study are (1) to evaluate the effects of partial sleep deprivation compared to no sleep deprivation for improving response to 8 weeks of fluoxetine 20-40 mg treatment and (2) to examine the underlying sleep mechanisms of treatment response. Participants who are eligible for the study will be randomly assigned to one of three sleep schedules for a 2-week period while taking fluoxetine: no sleep deprivation (8 hours time in bed), late bedtime (6 hours time in bed, with 2 hour bedtime delay) or early risetime (6 hours time in bed, with 2 hour advancement of rise time). Participants will spend a total of 7 nights in our sleep laboratory and will be followed on fluoxetine for an 8-week period.
Interventions
BEHAVIORALSleep scheduling
8 hours vs. 6 hours time in bed for two weeks, with either 2 hour advance of risetime, or 2 hour delay of bedtime
DRUGFluoxetine
20-40 mg fluoxetine daily for 8 weeks
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Between 18 and 65 years old * Current major depressive episode * Habitual TIB of 7 to \< 10 hours * No antidepressant medications for ≥ 2 weeks (4 weeks for MAOIs or longer acting antidepressants) * Score of at least 18 on the Hamilton Rating Scale of Depression
Exclusion criteria
* Alcohol or substance abuse/dependence in past 6 months * Current posttraumatic stress disorder or bulimia nervosa (past 6 months) * Lifetime history of bipolar I or II disorder, schizophrenia/other psychotic disorder, and anorexia nervosa * Trials of fluoxetine in the past 6 months * Medical disorders or pain syndromes that may affect sleep or are associated with significant depression (e.g. thyroid or Cushing's disease); history of head trauma with loss of consciousness of \> 5 minutes; history of seizures * Sleep disorders other than insomnia, such as sleep apnea and periodic limb movement disorder * Current use of prescription, over-the-counter, or naturopathic remedies for sleep (e.g., barbiturates, benzodiazepine agonists, nonbenzodiazepine hypnotics, analgesics) or depression (e.g., Sam-E, St. John's Wort) * Currently working evening or midnight shift (subjects who have recently traveled across multiple time zones will be included at the discretion of the PI). * Currently at risk for drowsy driving or employment that requires routine operation of transportation vehicles (e.g., truck/taxi driver, airline pilot) or hazardous equipment. * Known allergy, hypersensitivity or contraindication to study medication * Females: pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Rating Scale for Depression-17 Item Minus Sleep Items | Post-treatment (8 weeks) | Total score on a clinician-rated measure of depressive symptoms, minus 3 sleep items Total score range: 0-46. Higher scores represent more severe depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pittsburgh Sleep Quality Index | Baseline, 2 weeks and 8 weeks post-treatment | Self-report measure of sleep quality. The Pittsburgh Sleep Quality Index is a validated scale which measures self-reported sleep quality based on a wide variety of questions (duration, quality, disturbances, medication, etc.) and converts them to a scale which ranges from 0 to 21 where 6 or higher denotes poor sleep quality. |
| Change in EEG Sleep Measures I: Total Sleep Time | Baseline, 2 weeks, 8 weeks | Measurement of EEG activity during sleep using polysomnography: Total Sleep Time is the length of time from sleep onset to final wake up minus any wakefulness during the night. It reflects the total amount of time asleep during the night. |
| Change in EEG Sleep Measures II (Sleep Efficiency) | Baseline, 2 weeks, 8 weeks | Measurement of EEG activity during sleep using polysomnography: Sleep efficiency \[(total sleep time/time in bed)\*100\] |
| Quick Inventory of Depressive Symptoms (QIDS) | Post-treatment (8 weeks) | Patient-reported depression symptom severity at post-treatment, total score. Total scores range from 0 to 27. Higher scores represent more severe depression. |
| Change in Neurologic Functioning: Reaction Time | 0, 2, 8 weeks | Reaction Time is measured using a modified Go/No-go test of inhibitory control |
| Neurological Function (Emotional Perception) | 0 weeks, 2 weeks, 8 weeks | Emotional Perception is measured based on the percent of faces whose emotions are correctly identified using the Facial Emotion Perception Test (FEPT) |
| Change in Neuropsychological Functioning: Memory | Baseline, 2 weeks, 8 weeks | Change in different aspects of thinking (e.g., memory, attention, executive functioning) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| No Sleep Deprivation 8 hours time in bed plus medication
Sleep scheduling: 8 hours time in bed for two weeks
Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks | 19 |
| Late Bedtime Sleep Deprivation 6 hours time in bed plus medication
Sleep scheduling:6 hours time in bed for two weeks; bedtime delayed by 2 hours
Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks | 24 |
| Early Risetime Sleep Deprivation 6 hours time in bed plus medication
Sleep scheduling:6 hours time in bed for two weeks; risetime advanced by 2 hours
Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks | 25 |
| Total | 68 |
Baseline characteristics
| Characteristic | No Sleep Deprivation | Late Bedtime Sleep Deprivation | Early Risetime Sleep Deprivation | Total |
|---|---|---|---|---|
| Age, Continuous | 26.4 years STANDARD_DEVIATION 7.4 | 24.4 years STANDARD_DEVIATION 5.6 | 25.7 years STANDARD_DEVIATION 7 | 25.4 years STANDARD_DEVIATION 6.6 |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 14 Participants | 34 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 11 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 5 / 24 | 0 / 25 |
| serious Total, serious adverse events | 0 / 19 | 0 / 24 | 0 / 25 |
Outcome results
Primary
Hamilton Rating Scale for Depression-17 Item Minus Sleep Items
Total score on a clinician-rated measure of depressive symptoms, minus 3 sleep items Total score range: 0-46. Higher scores represent more severe depression.
Time frame: Post-treatment (8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Sleep Deprivation | Hamilton Rating Scale for Depression-17 Item Minus Sleep Items | 6.1 units on a scale | Standard Deviation 6.7 |
| Late Bedtime Sleep Deprivation | Hamilton Rating Scale for Depression-17 Item Minus Sleep Items | 8.1 units on a scale | Standard Deviation 4.4 |
| Early Risetime Sleep Deprivation | Hamilton Rating Scale for Depression-17 Item Minus Sleep Items | 6.3 units on a scale | Standard Deviation 4.9 |
p-value: 0.202Mixed Models Analysis
Secondary
Change in EEG Sleep Measures II (Sleep Efficiency)
Measurement of EEG activity during sleep using polysomnography: Sleep efficiency \[(total sleep time/time in bed)\*100\]
Time frame: Baseline, 2 weeks, 8 weeks
Population: Subsequent rows have lower numbers of participants analyzed due to participant flow and/or unusable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Week 2 | 90.7824 percent of sleep time | Standard Deviation 5.29745 |
| No Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Baseline | 89.7005 percent of sleep time | Standard Deviation 12.6282 |
| No Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Week 8 | 91.6153 percent of sleep time | Standard Deviation 4.03518 |
| Late Bedtime Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Week 2 | 93.3322 percent of sleep time | Standard Deviation 4.97614 |
| Late Bedtime Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Baseline | 91.6829 percent of sleep time | Standard Deviation 7.58117 |
| Late Bedtime Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Week 8 | 88.9224 percent of sleep time | Standard Deviation 11.09279 |
| Early Risetime Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Baseline | 92.8248 percent of sleep time | Standard Deviation 4.01214 |
| Early Risetime Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Week 8 | 90.3838 percent of sleep time | Standard Deviation 7.1743 |
| Early Risetime Sleep Deprivation | Change in EEG Sleep Measures II (Sleep Efficiency) | Week 2 | 92.9082 percent of sleep time | Standard Deviation 4.01214 |
Secondary
Change in EEG Sleep Measures I: Total Sleep Time
Measurement of EEG activity during sleep using polysomnography: Total Sleep Time is the length of time from sleep onset to final wake up minus any wakefulness during the night. It reflects the total amount of time asleep during the night.
Time frame: Baseline, 2 weeks, 8 weeks
Population: Number of participants analyzed decreases in subsequent rows, as some participants dropped out or had unusable data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Week 2 | 435.382 minutes | Standard Deviation 25.7206 |
| No Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Baseline | 430.132 minutes | Standard Deviation 60.923 |
| No Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Week 8 | 439.6 minutes | Standard Deviation 19.5231 |
| Late Bedtime Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Week 2 | 337.75 minutes | Standard Deviation 24.69 |
| Late Bedtime Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Baseline | 439.208 minutes | Standard Deviation 36.3375 |
| Late Bedtime Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Week 8 | 428.264 minutes | Standard Deviation 54.457 |
| Early Risetime Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Baseline | 444.040 minutes | Standard Deviation 19.7283 |
| Early Risetime Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Week 8 | 433.333 minutes | Standard Deviation 35.0347 |
| Early Risetime Sleep Deprivation | Change in EEG Sleep Measures I: Total Sleep Time | Week 2 | 332.909 minutes | Standard Deviation 17.048 |
Secondary
Change in Neurologic Functioning: Reaction Time
Reaction Time is measured using a modified Go/No-go test of inhibitory control
Time frame: 0, 2, 8 weeks
Population: At some time points, some participants did not show up to appointments or allow a particular test to be employed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 2 | 493.2579 milliseconds | Standard Deviation 58.64806 |
| No Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 0 (Baseline) | 499.1545 milliseconds | Standard Deviation 65.66508 |
| No Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 8 | 483.7349 milliseconds | Standard Deviation 55.33537 |
| Late Bedtime Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 2 | 519.8196 milliseconds | Standard Deviation 60.68815 |
| Late Bedtime Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 0 (Baseline) | 528.3513 milliseconds | Standard Deviation 135.86747 |
| Late Bedtime Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 8 | 557.1635 milliseconds | Standard Deviation 188.22995 |
| Early Risetime Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 0 (Baseline) | 470.2942 milliseconds | Standard Deviation 61.65017 |
| Early Risetime Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 8 | 500.1197 milliseconds | Standard Deviation 148.46524 |
| Early Risetime Sleep Deprivation | Change in Neurologic Functioning: Reaction Time | Week 2 | 472.7244 milliseconds | Standard Deviation 56.51599 |
Secondary
Change in Neuropsychological Functioning: Memory
Change in different aspects of thinking (e.g., memory, attention, executive functioning)
Time frame: Baseline, 2 weeks, 8 weeks
Population: At some time points, some participants did not show up to appointments or allow a particular test to be employed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Week 2 | 76.647 words | Standard Deviation 15.0829 |
| No Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Baseline | 77.118 words | Standard Deviation 17.1569 |
| No Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Week 8 | 73.923 words | Standard Deviation 12.1481 |
| Late Bedtime Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Week 2 | 81.529 words | Standard Deviation 10.1311 |
| Late Bedtime Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Baseline | 74.938 words | Standard Deviation 10.2337 |
| Late Bedtime Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Week 8 | 79.733 words | Standard Deviation 7.4399 |
| Early Risetime Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Baseline | 76.095 words | Standard Deviation 13.4458 |
| Early Risetime Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Week 8 | 81.200 words | Standard Deviation 14.1885 |
| Early Risetime Sleep Deprivation | Change in Neuropsychological Functioning: Memory | Week 2 | 77.400 words | Standard Deviation 13.8579 |
Secondary
Neurological Function (Emotional Perception)
Emotional Perception is measured based on the percent of faces whose emotions are correctly identified using the Facial Emotion Perception Test (FEPT)
Time frame: 0 weeks, 2 weeks, 8 weeks
Population: At some time points, some participants did not show up to appointments or allow a particular test to be employed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Sleep Deprivation | Neurological Function (Emotional Perception) | Week 2 | 83.08 percentage of emotions accurately ID'ed | Standard Deviation 6.938 |
| No Sleep Deprivation | Neurological Function (Emotional Perception) | 0 weeks (Baseline) | 83.54 percentage of emotions accurately ID'ed | Standard Deviation 10.549 |
| No Sleep Deprivation | Neurological Function (Emotional Perception) | Week 8 | 85.95 percentage of emotions accurately ID'ed | Standard Deviation 8.585 |
| Late Bedtime Sleep Deprivation | Neurological Function (Emotional Perception) | Week 2 | 88.15 percentage of emotions accurately ID'ed | Standard Deviation 6.159 |
| Late Bedtime Sleep Deprivation | Neurological Function (Emotional Perception) | 0 weeks (Baseline) | 86.24 percentage of emotions accurately ID'ed | Standard Deviation 6.721 |
| Late Bedtime Sleep Deprivation | Neurological Function (Emotional Perception) | Week 8 | 89.15 percentage of emotions accurately ID'ed | Standard Deviation 4.724 |
| Early Risetime Sleep Deprivation | Neurological Function (Emotional Perception) | 0 weeks (Baseline) | 88.83 percentage of emotions accurately ID'ed | Standard Deviation 7.321 |
| Early Risetime Sleep Deprivation | Neurological Function (Emotional Perception) | Week 8 | 87.74 percentage of emotions accurately ID'ed | Standard Deviation 4.708 |
| Early Risetime Sleep Deprivation | Neurological Function (Emotional Perception) | Week 2 | 88.75 percentage of emotions accurately ID'ed | Standard Deviation 7.099 |
Secondary
Pittsburgh Sleep Quality Index
Self-report measure of sleep quality. The Pittsburgh Sleep Quality Index is a validated scale which measures self-reported sleep quality based on a wide variety of questions (duration, quality, disturbances, medication, etc.) and converts them to a scale which ranges from 0 to 21 where 6 or higher denotes poor sleep quality.
Time frame: Baseline, 2 weeks and 8 weeks post-treatment
Population: At some time points, some participants did not show up to appointments or allow a particular test to be employed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Sleep Deprivation | Pittsburgh Sleep Quality Index | Week 8 | 4.86 units on a scale | Standard Deviation 2.248 |
| No Sleep Deprivation | Pittsburgh Sleep Quality Index | Week 2 | 5.23 units on a scale | Standard Deviation 2.204 |
| No Sleep Deprivation | Pittsburgh Sleep Quality Index | Baseline | 6.00 units on a scale | Standard Deviation 2.828 |
| Late Bedtime Sleep Deprivation | Pittsburgh Sleep Quality Index | Week 8 | 6.23 units on a scale | Standard Deviation 2.713 |
| Late Bedtime Sleep Deprivation | Pittsburgh Sleep Quality Index | Baseline | 8.67 units on a scale | Standard Deviation 2.839 |
| Late Bedtime Sleep Deprivation | Pittsburgh Sleep Quality Index | Week 2 | 6.07 units on a scale | Standard Deviation 2.615 |
| Early Risetime Sleep Deprivation | Pittsburgh Sleep Quality Index | Week 2 | 5.50 units on a scale | Standard Deviation 2.312 |
| Early Risetime Sleep Deprivation | Pittsburgh Sleep Quality Index | Baseline | 6.85 units on a scale | Standard Deviation 3.236 |
| Early Risetime Sleep Deprivation | Pittsburgh Sleep Quality Index | Week 8 | 6.33 units on a scale | Standard Deviation 2.944 |
Secondary
Quick Inventory of Depressive Symptoms (QIDS)
Patient-reported depression symptom severity at post-treatment, total score. Total scores range from 0 to 27. Higher scores represent more severe depression.
Time frame: Post-treatment (8 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Sleep Deprivation | Quick Inventory of Depressive Symptoms (QIDS) | 5.3 units on a scale | Standard Deviation 4.7 |
| Late Bedtime Sleep Deprivation | Quick Inventory of Depressive Symptoms (QIDS) | 6.9 units on a scale | Standard Deviation 3.3 |
| Early Risetime Sleep Deprivation | Quick Inventory of Depressive Symptoms (QIDS) | 6.7 units on a scale | Standard Deviation 4.5 |