Circadian Effects of Escitalopram
Condition: Depression
MeSH terms: Depression
Study type: Interventional

Summary: 
      The goal of the study is to obtain preliminary data that will test whether the antidepressant
      medication escitalopram resets the body clock: a collection of nerve cells in the brain that
      control the timing of many body processes. The study will also test whether the improvement
      in depression symptoms with escitalopram correlates with the degree to which the timing of
      the body clock is properly aligned with the timing of sleep.
    

Detailed description: 
      Background: The human biological clock (circadian pacemaker) has long been thought to play a
      role in non-seasonal depression. A connection is suggested by the demonstration of 24-hour
      rhythms in mood, subjective and objective changes in sleep with depression, and reports of
      changes in the timing and amplitude of biological rhythms in depression. Furthermore, it is
      known that the neurotransmitter serotonin has a significant role in regulating biological
      rhythms and that drugs that act on serotonin (such as some antidepressants) are able to reset
      the biological clock in animals.

      Objective: The aim of the study is to obtain preliminary data that will test whether the
      antidepressant medication escitalopram has a resetting effect on the human biological clock
      and whether the improvement in depression symptoms with escitalopram correlates with the
      degree to which the timing of the biological clock is realigned with the timing of sleep.

      Design: 14-16-week, fixed dose (after titration), open label trial.

      Setting and Subjects: 50 individuals will be screened for participation. 15 individuals with
      unipolar, non-seasonal depression will be studied over 1 year.

      Intervention: Subjects will first complete a one week, single-blind placebo lead-in phase.
      Subjects will then receive escitalopram for 8 weeks (10 mg/day for the first 2 weeks of
      treatment and then 20mg/day for the remaining 6 weeks of treatment).

      Measurements: Subjects will keep a sleep diary and wear a wrist activity monitor throughout
      the study to document the timing and quality of sleep. On two occasions (end of placebo week
      and end of last treatment week) blood and/or saliva will be sampled every 30 minutes for 7
      hours and the resulting samples will be assayed for melatonin. The onset of melatonin
      secretion (dim light melatonin onset or DLMO) will be used to mark the timing of the
      biological clock (circadian phase). Circadian misalignment will be measured using the time
      interval between the DLMO and the average midsleep of the prior week (phase angle difference
      or PAD). Mood will be assessed throughout the study using the Hamilton Depression Rating
      Scale (HAM-D) as well as the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory
      (BAI).
    

Intervention name(s): placebo/escitalopram
Intervention type(s): Drug
Intervention description(s): Subjects will first complete a one week, single-blind placebo lead in phase. Subjects will then receive escitalopram for 8 weeks. Subjects will receive 10 mg/day for the first 2 weeks of active treatment, and then 20 mg/day for the remaining 6 weeks of treatment. Medication will be dispensed on a weekly basis.
Other intervention name(s): Lexapro; escitalopram
Intervention MeSH terms: Dexetimide; Citalopram; Escitalopram
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science