Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT01545843
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arms: 3
• Duration (Months): 45
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The purpose of the study is to determine whether changing sleep patterns improves response to an antidepressant medication.

Condition or Disease	Intervention/Treatment	Phase
Depression	Behavioral: Sleep scheduling; Drug: Fluoxetine	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: No sleep deprivation Sleep scheduling plus fluoxetine. 8 hours time in bed for two weeks plus fluoxetine for 8 weeks	Behavioral: Sleep 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; Drug: Fluoxetine; 20-40 mg fluoxetine daily for 8 weeks; Other Names: Prozac
Experimental: Late bedtime sleep deprivation Sleep scheduling plus fluoxetine. 6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Bedtime delayed by 2 hours.	Behavioral: Sleep 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; Drug: Fluoxetine; 20-40 mg fluoxetine daily for 8 weeks; Other Names: Prozac
Experimental: Early risetime sleep deprivation Sleep scheduling plus fluoxetine. 6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Risetime advanced by 2 hours.	Behavioral: Sleep 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; Drug: Fluoxetine; 20-40 mg fluoxetine daily for 8 weeks; Other Names: Prozac

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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]

5. Change in Neuropsychological Functioning: Memory [Baseline, 2 weeks, 8 weeks]

   Change in different aspects of thinking (e.g., memory, attention, executive functioning)

6. Change in Neurologic Functioning: Reaction Time [0, 2, 8 weeks]

   Reaction Time is measured using a modified Go/No-go test of inhibitory control

7. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan

Investigators

• Principal Investigator: J. Todd Arnedt, Ph.D., University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: J. Todd Arnedt, Assistant Professor of Psychiatry, University of Michigan
• ClinicalTrials.gov Identifier: NCT01545843
• Other Study ID Numbers: R01MH077690
• First Posted: Mar 7, 2012
• Last Update Posted: Dec 8, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by J. Todd Arnedt, Assistant Professor of Psychiatry, University of Michigan: depression; sleep; treatment
• Additional relevant MeSH terms: Sleep Deprivation; Depression; Depressive Disorder; Fluoxetine

Study Results

Participant Flow

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed for two weeks plus fluoxetine for 8 weeks	6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Bedtime delayed by 2 hours.	6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Rise time advanced by 2 hours.
Period Title: Overall Study
STARTED	19	24	25
COMPLETED	16	17	21
NOT COMPLETED	3	7	4

Baseline Characteristics

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation	Total
Arm/Group Description	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	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	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	Total of all reporting groups
Overall Participants	19	24	25	68
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.4 (7.4)	24.4 (5.6)	25.7 (7.0)	25.4 (6.6)
Sex: Female, Male (Count of Participants)
Female	7 36.8%	13 54.2%	14 56%	34 50%
Male	12 63.2%	11 45.8%	11 44%	34 50%

Outcome Measures

1. Primary Outcome

Title	Hamilton Rating Scale for Depression-17 Item Minus Sleep Items
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours time in bed for 2 weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay in bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance in risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	19	24	25
Mean (Standard Deviation) [units on a scale]	6.1 (6.7)	8.1 (4.4)	6.3 (4.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	No Sleep Deprivation, Late Bedtime Sleep Deprivation, Early Risetime Sleep Deprivation
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.202
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Quick Inventory of Depressive Symptoms (QIDS)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours vs. 6 hours time in bed for two weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay of bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance of risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	19	24	25
Mean (Standard Deviation) [units on a scale]	5.3 (4.7)	6.9 (3.3)	6.7 (4.5)

3. Secondary Outcome

Title	Pittsburgh Sleep Quality Index
Description	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

Outcome Measure Data

Analysis Population Description

At some time points, some participants did not show up to appointments or allow a particular test to be employed.

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours vs. 6 hours time in bed for two weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay of bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance of risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	14	14	15
Baseline	6.00 (2.828)	8.67 (2.839)	6.85 (3.236)
Week 2	5.23 (2.204)	6.07 (2.615)	5.50 (2.312)
Week 8	4.86 (2.248)	6.23 (2.713)	6.33 (2.944)

4. Secondary Outcome

Title	Change in EEG Sleep Measures I: Total Sleep Time
Description	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

Outcome Measure Data

Analysis Population Description

Number of participants analyzed decreases in subsequent rows, as some participants dropped out or had unusable data.

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours time in bed for 2 weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay in bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance in risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	19	24	25
Baseline	430.132 (60.9230)	439.208 (36.3375)	444.040 (19.7283)
Week 2	435.382 (25.7206)	337.75 (24.69)	332.909 (17.0480)
Week 8	439.6 (19.5231)	428.264 (54.4570)	433.333 (35.0347)

5. Secondary Outcome

Title	Change in EEG Sleep Measures II (Sleep Efficiency)
Description	Measurement of EEG activity during sleep using polysomnography: Sleep efficiency [(total sleep time/time in bed)*100]
Time Frame	Baseline, 2 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

Subsequent rows have lower numbers of participants analyzed due to participant flow and/or unusable data.

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours vs. 6 hours time in bed for two weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay of bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance of risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	19	24	25
Baseline	89.7005 (12.62820)	91.6829 (7.58117)	92.8248 (4.01214)
Week 2	90.7824 (5.29745)	93.3322 (4.97614)	92.9082 (4.01214)
Week 8	91.6153 (4.03518)	88.9224 (11.09279)	90.3838 (7.17430)

6. Secondary Outcome

Title	Change in Neuropsychological Functioning: Memory
Description	Change in different aspects of thinking (e.g., memory, attention, executive functioning)
Time Frame	Baseline, 2 weeks, 8 weeks

Outcome Measure Data

Analysis Population Description

At some time points, some participants did not show up to appointments or allow a particular test to be employed.

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours vs. 6 hours time in bed for two weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay of bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance of risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	17	17	21
Baseline	77.118 (17.1569)	74.938 (10.2337)	76.095 (13.4458)
Week 2	76.647 (15.0829)	81.529 (10.1311)	77.400 (13.8579)
Week 8	73.923 (12.1481)	79.733 (7.4399)	81.200 (14.1885)

7. Secondary Outcome

Title	Change in Neurologic Functioning: Reaction Time
Description	Reaction Time is measured using a modified Go/No-go test of inhibitory control
Time Frame	0, 2, 8 weeks

Outcome Measure Data

Analysis Population Description

At some time points, some participants did not show up to appointments or allow a particular test to be employed.

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours time in bed for 2 weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay in bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance in risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	17	17	21
Week 0 (Baseline)	499.1545 (65.66508)	528.3513 (135.86747)	470.2942 (61.65017)
Week 2	493.2579 (58.64806)	519.8196 (60.68815)	472.7244 (56.51599)
Week 8	483.7349 (55.33537)	557.1635 (188.22995)	500.1197 (148.46524)

8. Secondary Outcome

Title	Neurological Function (Emotional Perception)
Description	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

Outcome Measure Data

Analysis Population Description

At some time points, some participants did not show up to appointments or allow a particular test to be employed.

Arm/Group Title	No Sleep Deprivation	Late Bedtime Sleep Deprivation	Early Risetime Sleep Deprivation
Arm/Group Description	8 hours time in bed plus medication Sleep scheduling: 8 hours time in bed for 2 weeks Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour delay in bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks	6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, with 2 hour advance in risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
Measure Participants	17	17	21
0 weeks (Baseline)	83.54 (10.549)	86.24 (6.721)	88.83 (7.321)
Week 2	83.08 (6.938)	88.15 (6.159)	88.75 (7.099)
Week 8	85.95 (8.585)	89.15 (4.724)	87.74 (4.708)

Adverse Events

Adverse Event Reporting Description	Adverse events judged to be related to the study and of moderate or greater severity
Arm/Group Title	No Sleep Deprivation		Late Bedtime Sleep Deprivation		Early Risetime Sleep Deprivation
Arm/Group Description	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		6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, two hour delay of bedtime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks		6 hours time in bed plus medication Sleep scheduling: 6 hours time in bed for two weeks, two hour advance of risetime Fluoxetine: 20-40 mg fluoxetine daily for 8 weeks
All Cause Mortality
	No Sleep Deprivation		Late Bedtime Sleep Deprivation		Early Risetime Sleep Deprivation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	No Sleep Deprivation		Late Bedtime Sleep Deprivation		Early Risetime Sleep Deprivation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/24 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	No Sleep Deprivation		Late Bedtime Sleep Deprivation		Early Risetime Sleep Deprivation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		5/24 (20.8%)		0/25 (0%)
Gastrointestinal disorders
Medication side effects	0/19 (0%)	0	3/24 (12.5%)	3	0/25 (0%)	0
Psychiatric disorders
Mood worsening	0/19 (0%)	0	2/24 (8.3%)	2	0/25 (0%)	0

Limitations/Caveats

Sample is largely young, healthy adults

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.