The Role of Dopamine Metabolism in the Antidepressant Effects of Sleep Deprivation and Sertraline in Depressed Patients

This study evaluates the efficacy of sleep deprivation treatment in accelerating antidepressant responses when administered during the first week of medications and augmenting a sustained response with chronobiological interventions. Sleep deprivation and chronobiological augmentation may offer a rapid and sustained antidepressant response in mood disorder patients treated with medication, sleep deprivation, bright light therapy and sleep phase advance compared with medication only. The chronobiological treatment is rapid, non-invasive and has few side effects and could be of significant clinical benefit.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Major Depressive Disorder
• Intervention / Treatment: Other: chronobiological augmentation; Drug: sertraline, lithium; Radiation: one night of sleep deprivation and two FDG PET scans

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • La Jolla, California, United States, 92093 - 0603
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Inclusion criteria include:

1. Subjects must be English speaking
2. Subjects must have either bipolar or unipolar depression diagnosis or be a normal control.
3. Subjects must be between : 18 to 75

Non-English speaking subjects will be excluded since scales for measuring depression have not been validated in languages other than English.

Exclusion Criteria:

Exclusion criteria include:

1. Suicidality, or psychosis
2. Unstable medical conditions
3. Epilepsy, serious head injury, or other significant neurological disorders
4. Dementia, mental retardation (moderate or severe), coma
5. Prior exposure to radiation which might cause the subject to exceed standard guidelines
6. Substance abuse or alcoholism in the past six months
7. Unreliability or inability to adhere to the requirements of the study
8. Irregular sleep-wake schedules (nightshift, jet lag)
9. Use of CNS medications which may affect sleep or functional brain imaging (i.e., use of sleeping pills, antidepressants or other mood stabilizers or other medications which may affect the sleep EEG)
10. Sleep apnea, periodic limb movements of sleep, narcolepsy, circadian sleep phase disorders
11. Donation or loss of blood (>400 ml) within the past month
12. Current or very recent intercurrent illnesses, painful conditions or other disorders, which in the judgement of the investigators, might invalidate the scientific goals of the study or pose undesirable difficulties or risks for the subject.
13. Hamilton Rating Scale of Depression (HRSD-17 items)<17 unless subject is a normal control subject.
14. Pregnancy or breast feeding
15. Individuals who would be unable to undergo a magnetic resonance imaging (MRI) scan, for example, individuals who suffer from claustrophobia, or who have metal clips in their body.
16. Unable to cease taking psychoactive medications which are not part of this protocol (2-5 weeks) prior to PET scans.
17. Patients with previous history of significant adverse reactions to sertraline or sertraline-like drugs or other SSRI's such as Paxil or Prozac
18. Subjects with diagnosis of eating disorder/bulimia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MDD Mechanism	Radiation: one night of sleep deprivation and two FDG PET scans; MDD Mechanism Only depressed subjects will have two FDG PET scans consisting of a baseline FDG PET scan and a sleep deprived FDG PET scan. One night of regular sleep,one night of sleep deprivation and one night of recovery sleep for a total of four nights at a sleep laboratory facility.
Experimental: Chronobiological augmentation; chronobiological augmentation group	Other: chronobiological augmentation; Sleep deprivation for one night, Chronobiological augmentation consists of partial sleep phase advance for three nights and Light therapy for two hours for three days
Experimental: Medication only; medication only group	Drug: sertraline, lithium; Antidepressant, Subjects will be started on a serotonin specific reuptake inhibitor (SSRI), sertraline 100 mg (50mg hs x 2) daily or other SSRI's such as Paxil 20 mg or Prozac 20 mg daily and continue treatment for seven weeks. Mood stabilizer, subjects will be treated with lithium 450 mg twice a day or another mood stabilizer such as depakote or valproate and continue treatment for seven weeks.; Other Names: Zoloft; Lithium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Score on the Hamilton Rating Score for Depression (HRSD) - 21 Item Version	Difference in HRSD between the chronobiological augmentation therapy and medication only groups across the first 7 days, and up to 7 weeks of treatment. The 21-item HRSD has a range of 0 to 66, with a higher score indicating more severe depression.	within the first seven days up to 7 weeks (plus or minus 1 day) after sleep deprivation and chronobiological therapy

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: University of California, San Diego
• Investigators: Study Chair: Barry F Chaitin, M.D., University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2001
• Primary Completion (Actual): December 9, 2011
• Study Completion (Actual): December 9, 2011

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: December 26, 2007
• First Posted (Estimated): December 27, 2007

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: depression; antidepressant; Sleep deprivation; chronobiological
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Mood Disorders; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Bipolar and Related Disorders; Depressive Disorder; Bipolar Disorder; Depressive Disorder, Major; Sleep Deprivation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antimanic Agents; Selective Serotonin Reuptake Inhibitors; Sertraline; Lithium Carbonate
• Other Study ID Numbers: 20011616

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No