Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression

• Change in Self-rated Depression Symptoms: Quick Inventory of Depressive Symptoms [ Time Frame: Baseline, 2 weeks, 8 weeks ] [ Designated as safety issue: No ]
  Patient-reported depressive symptoms
• Change in Sleep Quality: Pittsburgh Sleep Quality Index [ Time Frame: Baseline, 2 weeks, 8 weeks ] [ Designated as safety issue: No ]
  Self-report of sleep quality
• Change in EEG Sleep measures [ Time Frame: Baseline, 2 weeks, 8 weeks ] [ Designated as safety issue: No ]
  Measurement of EEG activity during sleep using polysomnography
• Change in Neuropsychological Functioning [ Time Frame: Baseline, 2 weeks, 8 weeks ] [ Designated as safety issue: Yes ]
  Change in multiple domains of neuropsychological functioning (e.g., memory, attention, executive functioning)

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

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 early and late 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 keep one of 3 sleep schedules for a 2-week period while taking fluoxetine: no sleep deprivation (8 hours time in bed), early partial sleep deprivation (6 hours time in bed, with bedtime delayed by 2 hours), or late partial sleep deprivation (6 hours time in bed, with wake time advanced by 2 hours). Participants will spend a total of 7 nights in our sleep laboratory and will be followed on fluoxetine for an 8-week period.

• Behavioral: Sleep scheduling
  8 hours vs. 6 hours time in bed for two weeks
• Drug: Fluoxetine
  20-40 mg fluoxetine daily for 8 weeks
  Other Name: Prozac

• Active Comparator: No sleep deprivation
  8 hours time in bed plus medication
  Interventions:

  • Behavioral: Sleep scheduling
  • Drug: Fluoxetine
• Active Comparator: Early sleep deprivation
  6 hours time in bed plus medication
  Interventions:

  • Behavioral: Sleep scheduling
  • Drug: Fluoxetine
• Active Comparator: Late sleep deprivation
  6 hours time in bed plus medication
  Interventions:

  • Behavioral: Sleep scheduling
  • Drug: Fluoxetine

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