Repeated Partial Sleep Deprivation to Augment SSRI Response in Depression

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.

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