The Effects of Sleep Deprivation on Antidepressant Response

The Effects of Sleep Deprivation on Antidepressant Response in Geriatric Depression: Neurometabolic Substrates Studied With PET

This study will use positron emission tomography (PET) to examine the effect of sleep deprivation on brain function.

Study Overview

• Status: Completed
• Conditions: Unipolar Depression
• Intervention / Treatment: Behavioral: total sleep deprivation; Procedure: PET imaging

Detailed Description

This study seeks to better understand the effect of sleep deprivation (TSD) on brain function using Positron Emission Tomography (PET). PET is an established research procedure that produces images of the brain. The purpose of these images is to show changes in brain activity associated with sleep deprivation. The neurochemical mechanisms underlying the TSD acceleration of antidepressant efficacy have not been identified. An understanding of these neurochemical processes may lead to the development of pharmacologic strategies that would accelerate antidepressant response or more directly to the development of antidepressant treatments that are more efficacious.

This study will be conducted in collaboration with Dr. Charles Reynolds' ongoing protocol "Geriatric Depression: Neurobiology of Treatment" (IRB #970356). The impetus for the clinical studies is the finding that the clinical response to antidepressant treatment in geriatric depressed patients is delayed, with the median time to remission reported as up to 12 weeks. Thus, the development of a strategy to accelerate treatment response would represent a substantial contribution to the treatment of geriatric depression. One approach that has been reported to accelerate antidepressant response in mid-life depression is one night of total sleep deprivation (TSD) prior to initiating antidepressant treatment. TSD has also been shown to improve mood in depressed patients, the response to TSD may distinguish subsequent treatment responders from non-responders and depressive relapse may occur after naps or a night of recovery sleep. The neurochemical mechanisms underlying the TSD acceleration of antidepressant efficacy have not been identified. An understanding of these neurochemical processes may lead to the development of pharmacologic strategies that would accelerate antidepressant response or more directly to the development of antidepressant treatments that are more efficacious.

Advancements in brain imaging technology and radiotracer chemistry have made it possible to measure metabolic activity and specific neurochemical mechanisms using Positron Emission Tomography (PET). The proposed studies represent the initial step in characterizing the neurochemical alterations produced by TSD and the impact of TSD on antidepressant response by TSD in geriatric depressed patients using PET and a radiotracer for brain glucose metabolism, [18F]-2deoxy-2-fluoro-D-glucose ([18F]-2DG). Having established the regional metabolic alterations associated with sleep deprivation and recovery sleep in patients who are subsequent treatment responders and compared the metabolic changes with treatment non-responders, future studies will be undertaken using neuroreceptor radiotracers to define the specific neurochemical pathways subserving the regional pattern of metabolic alterations. The glucose metabolic response to sleep deprivation in mid-life depression has been investigated at the UPMC PET Facility and at other institutions (e.g. Dube et al., in preparation, Wu et al., 1991, 1992). The studies performed in the geriatric depressed patients will be compared with the PET studies conducted in mid-life depressed patients to assess the contribution of the aging process to the neurometabolic response to sleep.

For information on related studies, please follow these links:

http://clinicaltrials.gov/show/NCT00177294

http://clinicaltrials.gov/show/NCT00178035

• Study Type: Interventional
• Enrollment: 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients:

• DSM-IV criteria for current major depressive disorder
• Score of 15 or higher on the HRSD (17 item)
• Score of 17 or higher on the Folstein Mini-Mental Status Exam

Control Subjects:

-No history of psychiatric disorder or neurological illness

Exclusion Criteria:

Patients:

• lifetime diagnosis of any psychotic disorder
• bipolar disorder
• alcohol or drug abuse within the last 6 months
• No contraindication to SSRI therapy
• History of seizure disorder

Both Patient and Control Subjects:

-Current diagnosis of diabetes or significantly altered plasma glucose levels

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To gain an understanding of the neurochemical processes that may lead to development of pharmacologic strategies that would accelerate antidepressant response or more directly to the development of antidepressant treatments.
PET study
Regional glucose metabolic rates and regional [18F]-altanserin binding
MRI scan

Secondary Outcome Measures

Outcome Measure
Hamilton Depression Rating Scale
Beck Depression Inventory
SCID
Profile of Mood States
Serum anticholinergicity and paroxetine blood levels
Folstein Mini-Mental State Exam

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Charles F Reynolds III, M.D., University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: February 1, 1999
• Study Completion: April 1, 2003

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): August 2, 2013
• Last Update Submitted That Met QC Criteria: July 31, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: imaging; depression; PET; elderly; sleep deprivation; late life
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Depression; Depressive Disorder; Sleep Deprivation
• Other Study ID Numbers: R01MH037869-03 (U.S. NIH Grant/Contract); DATR A4-GPS; 980753