Does Fluoxetine Have an Effect on the CNS CRF Systems in Women Abused in Childhood?

Does Fluoxetine Reverse the Effects of Early Life Stress on the CNS Corticotropin-Releasing Factor System and Improve Psychological and Neuroendocrine Function?: A Therapy Outcome Study in Women With Childhood Abuse Experiences

The primary objective of this project is to determine whether treatment with the SSRI, fluoxetine versus placebo reverses alterations in the central CRF system induced by early life stress experiences (i.e. childhood sexual and/or physical abuse) in cases with and without major depression. We also evaluate whether neuroendocrine changes after SSRI treatment correlate with clinical improvement.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Fluoxetine

Detailed Description

We compare indices of central CRF activity (i.e. ACTH and cortisol response to CRF stimulation test) before and after 8 weeks of treatment with either fluoxetine or placebo between women with a history of childhood abuse (early life stress, ELS) and current major depression (ELS/MDD), women with a history of childhood abuse without major depression (ELS/non-MDD), and women without a history of childhood abuse and major depression (non-ELS/MDD). Changes in neuroendocrine responses to CRF are correlated with psychological outcome measures. We hypothesize that treatment with fluoxetine will normalize altered neuroendocrine responsiveness in cases with ELS and that this normalization will be correlated with improvement of symptoms of depression and anxiety.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Department of Psychiatry and Behavioral Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. For all subjects female gender;
2. For subjects assigned to the MDD groups, current DSM-IV diagnosis of MDD;
3. For subjects assigned to the early-life stress group, repeated (once per month or more for at least year) sexual or physical abuse before the age of 12 years by a perpetrator at least 5 years older at the time;
4. For all subjects, age of 18 to 45 years;
5. Regular menstrual cycle and assessment in the early follicular phase as verified by sex steroid measures.

Exclusion Criteria:

1. For all subjects, gender identity disorders;
2. For all subjects assigned to non-MDD groups, DSM-IV diagnosis of current MDD;
3. For all subjects assigned to the group without early-life stress, major stress experiences before the age of 12 years, such as separation from parents, neglect, parental loss, accidents, severe illness or natural disaster;
4. For all subjects, significant medical illness, such as gastrointestinal, neurological, endocrine, cardiovascular, pulmonary, renal, hepatic, immunological or hematological disease, organic brain disease, or cancer as determined by history, physical examination, ECG, and laboratory tests;
5. Pregnancy or nursing;
6. For all subjects, past or current presence of psychotic symptoms or bipolar disorder;
7. For all subjects, current presence of psychoactive substance abuse/dependency or eating disorders;
8. For all subjects, hormonal medication;
9. For all subjects, psychotropic medication in the four weeks prior to study entry;
10. For all subjects, inability to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma ACTH and cortisol concentrations before and after administration of 1 microgram per kg ovine CRF	6 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Symptom Rating Scales for Depression, Anxiety and PTSD as well as general well-being	8 weeks

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Christine M Heim, PhD, Emory University-Dept. of Psychiatry and Behavioral Sciences

Study record dates

Study Major Dates

• Study Start: December 1, 1997
• Primary Completion (Actual): November 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 21, 2005

Study Record Updates

• Last Update Posted (Estimate): November 11, 2013
• Last Update Submitted That Met QC Criteria: November 8, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: CRF; HPA-axis; Early Life Stress
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: IRB00001850; B1Y-MC-X176 (Other Identifier: Other)