Circadian Effects of Escitalopram

Not Applicable

Completed

Conditions: Depression

Interventions: Drug: placebo/escitalopram

Registration Number: NCT01214044

Lead Sponsor: Oregon Health and Science University

Brief 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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 Complete Blood Count, Complete Metabolic Set, Thyroid Stimulating Hormone, 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study Drug	placebo/escitalopram	Subjects will have a total of 12 visits to Oregon Clinical \& Translational Research Institute at Oregon Health \& Science University over the 14-16 weeks of study. Subjects will first undergo an initial screening visit to determine eligibility. Subjects who meet criteria and agree to participate will then stop taking their current antidepressant medication (if applicable), during which time the study doctor and staff will conduct weekly mood assessments to ensure safety. Subjects will then have a study initiation/materials visit followed by 9 visits during treatment with placebo or escitalopram. A final post-study follow-up safety visit will be scheduled at the end of treatment.

Primary Outcome Measures

Name	Time	Method
Change in Dim Light Melatonin Onset	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)	The Dim Light Melatonin Onset (DLMO) is the time of the onset of melatonin secretion under dim light conditions using the equivalent thresholds of 10 pg/ml in plasma and 3 pg/ml in saliva. It is a marker of biological time. Data are provided in decimal and military time (e.g., 9:30 pm equals 21.50). This measure is used to determine if there was a change in the time of the dim light melatonin onset (DLMO) before treatment with escitalopram (at Study Visit 3) and after treatment with escitalopram (at Study Visit 11).

Secondary Outcome Measures

Name	Time	Method
Change in Phase Angle Difference (PAD)	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)	The PAD is the time interval (number of hours) between the Dim Light Melatonin Onset (DLMO) and the average midpoint of sleep during the prior week. Larger PADs indicate a longer time interval between the DLMO and midpoint of sleep. A negative change in PAD value indicates a shortening of the time interval from Study Visit 3 to Study Visit 11.
Change in Beck Depression Inventory II (BDI-II) Scores	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)	The BDI-II is the total score on the 21-question Beck Depression Inventory II questionnaire. Scores range from 0 to 63 with higher scores indicating worse symptoms of depression.
Change in Hamilton Depression Rating Scale (HAM-D) Scores	8 Weeks: Study Visit 3 (after 1 week of placebo) to study Visit 11 (after 8 weeks of escitalopram)	The HAM-D is the total score on the 21-question Hamilton Depression Rating Scale. Scores range from 0 to 53 with higher scores indicating worse symptoms of depression.