Circadian Effects of Escitalopram

Condition(s) targeted: Depression

Intervention: placebo/escitalopram (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Oregon Health and Science University

Official(s) and/or principal investigator(s):
Jonathan Emens, MD, Principal Investigator, Affiliation: Oregon Health and Science University

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.

Official title: Circadian Effects of Escitalopram

Study design: Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Primary outcome: Resetting effect of Escitalopram on the circadian pacemaker

Secondary outcome: Correlation between improvement in depression with Escitalopram and the degree of realignment between the timing of sleep and the timing of the biological clock.

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).

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 18-65 years old

- able to comply with requirements of the experimental protocol

- competent to sign informed consent

- have mild to severe major depressive disorder without psychotic features and without

a seasonal pattern

- currently be under the care of a licensed mental health care provider or primary care

physician

- Score > 7 when interviewed by a trained rater using the 21-Item Hamilton Depression

Scale (HAM-D)

- be in good physical health

- not be suicidal

- not be taking any other antidepressant medications besides escitalopram during the

study

- be free of antidepressant medications for 2-4 weeks prior to beginning the study

- not have a history of transmeridian travel or shift work in the past 2 months and

have no plans for transmeridian travel or shift work for the duration of the study

- be able to maintain a regular sleep wake schedule for the weeks one and nine of study

- women of childbearing potential must have a negative pregnancy test and practice an

acceptable method of birth control Exclusion Criteria:

- abnormal heart, liver, or kidney function

- significant laboratory abnormalities on CBC, Complete Metabolic Set, TSH, EKG, &

urinalysis

- shift work or transmeridian travel in the last 2 months

- current use of melatonin

- evidence of a primary sleep disorder by history

- women who are pregnant or lactating

- be taking medications with known sedative or stimulating effects or that would

interfere with the production of melatonin

Oregon Health & Science University, Portland, Oregon 97239, United States; Recruiting
Jonathan Emens, MD, Phone: 503-494-4677, Email: emensj@ohsu.edu
Alfrew Lewy, MD, PhD, Phone: (503) 494-7746, Email: lewy@ohsu.edu
Jonathan Emens, MD, Principal Investigator

Starting date: May 2008
Last updated: October 1, 2010