Metyrapone as Additive Treatment in Major Depression

This study has been completed.
Sponsor:
Information provided by:
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT00125554
First received: July 29, 2005
Last updated: August 11, 2005
Last verified: July 2005
  Purpose

The purpose of this study is to test whether metyrapone is an effective and safe augmenting agent in the treatment of major depression.


Condition Intervention Phase
Major Depressive Disorder
Drug: Metyrapone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo Controlled Trial of Metyrapone as Augmenting Agent in the Treatment of Major Depression

Resource links provided by NLM:


Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • Two psychometric criteria defined by the number of responders and time to onset-of-action. The number of responders was considered twice after 3 and 5 weeks by defining the treatment response as a 30% and 50% reduction
  • the course of concentrations of ACTH, cortisol, 11-deoxycortisol and DHEA.

Secondary Outcome Measures:
  • Other psychometric scores, demographic parameters and side effects were considered as secondary variables.

Estimated Enrollment: 63
Study Start Date: May 1998
Estimated Study Completion Date: July 2001
Detailed Description:

The investigators' understanding of the neuroendocrine pathophysiology of depression has made significant progress in recent years, which should help to develop new remedies. Alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis are the most consistent pathological endocrine findings in depression. Hence, attempts have been made to treat depression by directly targeting HPA-axis activity. Currently, three major pathways are investigated:

  • Administration of CRH-antagonists;
  • Administration of glucocorticoid-receptor-antagonists; and
  • Treatment with steroid-synthesis inhibitors like ketoconazole, aminogluthethimide or metyrapone.

The investigators' aim was to conduct the first prospective, randomized, placebo-controlled, double-blind clinical trial of metyrapone as additive treatment in depression. Metyrapone was preferred, since this compound inhibits selectively the 11β-hydroxylase and the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), thereby exerting direct effects within the central nervous system (CNS). The additive approach was applied because the intended inclusion of severely depressed patients made a pure placebo group ethically challenging. Furthermore, the continuous use of an antidepressant allowed a standardized follow up after the double-blind period.

The hypotheses to be tested were, whether metyrapone exerts potentiating effects during a standard antidepressant therapy and whether an earlier onset-of-action and an improved overall and sustained treatment response can be achieved. Since GR/MR distribution as well as 11β-HSD-1 activities are subject to sexual dimorphism in humans, the sample was prospectively stratified for gender and balanced for treatment with two selected serotonergic antidepressants, allowing further analysis of gender effects and neuroendocrine treatment effects.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of major depressive disorder; single or recurrent according to DSM-IV criteria (296.2 or 296.3)
  • A minimum baseline Hamilton score of 18 points on the Hamilton Rating Scale for Depression (HamD; 21-item version)
  • Age from 18 to 75 years
  • A drug free period of at least 5 days from antidepressants, antipsychotics, mood stabilizers and all other medications except for mild antihypertensive agents
  • A negative urinary drug screening diagnosis

Exclusion Criteria:

  • A current DSM-IV diagnosis for other axis I psychiatric disorders
  • Serious medical conditions, especially those associated with adrenal insufficiency
  • Pregnancy, nursing or refusal to use a reliable method of birth control in women.

Participants were randomly assigned to a study group if they met these criteria.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125554

Locations
Germany
Dept. of Psychiatry and Psychotherapy, UKE
Hamburg, Germany, 20246
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
Study Director: Holger Jahn, MD University Hospital Hamburg-Eppendorf, Germany
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00125554     History of Changes
Other Study ID Numbers: HH-PSY-ja-007
Study First Received: July 29, 2005
Last Updated: August 11, 2005
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
Clinical trial
double-blind
randomized placebo-controlled trial
metyrapone
Major Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Metyrapone
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014