Improving Sleep and Psychological Functioning in People With Depression and Insomnia

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT00247624
• Collaborator: National Institute of Mental Health (NIMH) (NIH), Sunovion (Industry), Philips Healthcare (Industry)
• Enrollment: 60
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Initiation and Maintenance Disorders; Depression	Drug: Eszopiclone; Drug: Fluoxetine; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hypnotics in the Treatment of Psychiatric Disorders
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Participants will receive treatment with eszopiclone and fluoxetine	Drug: Eszopiclone; Eszopiclone 3 mg every night for 8 weeks; Drug: Fluoxetine; Fluoxetine 20 mg every morning for 9 weeks
Active Comparator: B Participants will receive treatment with placebo and fluoxetine	Drug: Fluoxetine; Fluoxetine 20 mg every morning for 9 weeks; Drug: Placebo; Placebo every night for 8 weeks

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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 Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest University Health Sciences; Department of Psychiatry and Behavioral Medicine	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Institute of Mental Health (NIMH)
• Sunovion
• Philips Healthcare

Investigators

• Principal Investigator: W. Vaughn McCall, MD, MS, Wake Forest University Health Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

• McCall WV, Reboussin BA, Cohen W. Subjective measurement of insomnia and quality of life in depressed inpatients. J Sleep Res. 2000 Mar;9(1):43-8.
• Zammit GK, Weiner J, Damato N, Sillup GP, McMillan CA. Quality of life in people with insomnia. Sleep. 1999 May 1;22 Suppl 2:S379-85.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT00247624
• Other Study ID Numbers: R34MH070821; DSIR 83-ATSO; R34MH070821
• First Posted: Nov 2, 2005
• Last Update Posted: Aug 28, 2018
• Last Verified: Jul 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: Depression; Hypnotics; Sleep; Quality of Life; Insomnia; Suicide
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Depression; Depressive Disorder; Eszopiclone; Fluoxetine

Study Results

Participant Flow

Arm/Group Title	Fluoxetine (FLX) Plus Eszopiclone (ESZ)	FLX Plus Placebo
Arm/Group Description	Participants will receive treatment with eszopiclone and fluoxetine	Participants will receive treatment with placebo and fluoxetine
Period Title: Overall Study
STARTED	30	30
COMPLETED	25	26
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Fluoxetine (FLX) Plus Eszopiclone (ESZ)	FLX Plus Placebo	Total
Arm/Group Description	Participants will receive treatment with eszopiclone and fluoxetine	Participants will receive treatment with placebo and fluoxetine	Total of all reporting groups
Overall Participants	30	30	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	30 100%	30 100%	60 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.9 (11.7)	38.0 (12.5)	41.5 (12.5)
Sex: Female, Male (Count of Participants)
Female	20 66.7%	20 66.7%	40 66.7%
Male	10 33.3%	10 33.3%	20 33.3%
BASIS 32 DLRF (units) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units]	1.9 (0.7)	2.0 (0.7)	2.0 (0.7)

Outcome Measures

1. Primary Outcome

Title	Daily Living and Role Functioning (DLRF) Basis-32 Subscale Ratings
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluoxetine (FLX) Plus Eszopiclone (ESZ)	FLX Plus Placebo
Arm/Group Description	Participants will receive treatment with eszopiclone and fluoxetine	Participants will receive treatment with placebo and fluoxetine
Measure Participants	30	30
Mean (Standard Deviation) [units on a scale]	0.81 (0.64)	1.2 (0.72)

2. Primary Outcome

Title	Relation to Self/Others (RSO) Basis-32 Subscale Ratings
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluoxetine (FLX) Plus Eszopiclone (ESZ)	FLX Plus Placebo
Arm/Group Description	Participants will receive treatment with eszopiclone and fluoxetine	Participants will receive treatment with placebo and fluoxetine
Measure Participants	30	30
Mean (Standard Deviation) [units on a scale]	0.74 (0.71)	1.04 (0.77)

3. Primary Outcome

Title	Quality of Life Ratings, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluoxetine (FLX) Plus Eszopiclone (ESZ)	FLX Plus Placebo
Arm/Group Description	Participants will receive treatment with eszopiclone and fluoxetine	Participants will receive treatment with placebo and fluoxetine
Measure Participants	30	30
Mean (Standard Deviation) [units on a scale]	50.2 (8.11)	46.9 (9.0)

4. Secondary Outcome

Title	Insomnia Severity Index (ISI)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluoxetine (FLX) Plus Eszopiclone (ESZ)	FLX Plus Placebo
Arm/Group Description	Participants will receive treatment with eszopiclone and fluoxetine	Participants will receive treatment with placebo and fluoxetine
Measure Participants	30	30
Mean (Standard Deviation) [units on a scale]	21.1 (4)	20.2 (4.1)

Adverse Events

Arm/Group Title	Fluoxetine (FLX) Plus Eszopiclone (ESZ)		FLX Plus Placebo
Arm/Group Description	Participants will receive treatment with eszopiclone and fluoxetine		Participants will receive treatment with placebo and fluoxetine
All Cause Mortality
	Fluoxetine (FLX) Plus Eszopiclone (ESZ)		FLX Plus Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Serious Adverse Events
	Fluoxetine (FLX) Plus Eszopiclone (ESZ)		FLX Plus Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Fluoxetine (FLX) Plus Eszopiclone (ESZ)		FLX Plus Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.