Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression

Phase 2

Completed

Conditions: Depression

Interventions: Behavioral: Sleep scheduling
Drug: Fluoxetine

Registration Number: NCT01545843

Lead Sponsor: University of Michigan

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early risetime sleep deprivation	Sleep scheduling	Sleep scheduling plus fluoxetine. 6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Risetime advanced by 2 hours.
Late bedtime sleep deprivation	Sleep scheduling	Sleep scheduling plus fluoxetine. 6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Bedtime delayed by 2 hours.
No sleep deprivation	Sleep scheduling	Sleep scheduling plus fluoxetine. 8 hours time in bed for two weeks plus fluoxetine for 8 weeks
No sleep deprivation	Fluoxetine	Sleep scheduling plus fluoxetine. 8 hours time in bed for two weeks plus fluoxetine for 8 weeks
Late bedtime sleep deprivation	Fluoxetine	Sleep scheduling plus fluoxetine. 6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Bedtime delayed by 2 hours.
Early risetime sleep deprivation	Fluoxetine	Sleep scheduling plus fluoxetine. 6 hours time in bed for two weeks plus fluoxetine for 8 weeks. Risetime advanced by 2 hours.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 EEG Sleep Measures II (Sleep Efficiency)	Baseline, 2 weeks, 8 weeks	Measurement of EEG activity during sleep using polysomnography: Sleep efficiency \[(total sleep time/time in bed)\*100\]
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)
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 Neuropsychological Functioning: Memory	Baseline, 2 weeks, 8 weeks	Change in different aspects of thinking (e.g., memory, attention, executive functioning)
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.