Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression

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

Detailed Description
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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.

Official Title
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Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression

Conditions
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Depression

Intervention / Treatment
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* Behavioral: Sleep scheduling
* Drug: Fluoxetine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No sleep deprivation<br>Sleep scheduling plus fluoxetine. 8 hours time in bed for two weeks plus fluoxetine for 8 weeks | Behavioral: Sleep scheduling<br>* 8 hours vs. 6 hours time in bed for two weeks, with either 2 hour advance of risetime, or 2 hour delay of bedtime<br>Drug: Fluoxetine<br>* 20-40 mg fluoxetine daily for 8 weeks<br>* Other names: Prozac;|
| Experimental: Late bedtime sleep deprivation<br>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<br>* 8 hours vs. 6 hours time in bed for two weeks, with either 2 hour advance of risetime, or 2 hour delay of bedtime<br>Drug: Fluoxetine<br>* 20-40 mg fluoxetine daily for 8 weeks<br>* Other names: Prozac;|
| Experimental: Early risetime sleep deprivation<br>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<br>* 8 hours vs. 6 hours time in bed for two weeks, with either 2 hour advance of risetime, or 2 hour delay of bedtime<br>Drug: Fluoxetine<br>* 20-40 mg fluoxetine daily for 8 weeks<br>* Other names: Prozac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Post-treatment (8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Post-treatment (8 weeks) | 
| 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. | Baseline, 2 weeks and 8 weeks post-treatment | 
| 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. | Baseline, 2 weeks, 8 weeks | 
| 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] | Baseline, 2 weeks, 8 weeks | 
| Change in Neuropsychological Functioning: Memory | Change in different aspects of thinking (e.g., memory, attention, executive functioning) | Baseline, 2 weeks, 8 weeks | 
| Change in Neurologic Functioning: Reaction Time | Reaction Time is measured using a modified Go/No-go test of inhibitory control | 0, 2, 8 weeks | 
| 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) | 0 weeks, 2 weeks, 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, sleep, treatment