Metyrapone as Additive Treatment in Major Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00125554
Recruitment Status : Completed
First Posted : August 1, 2005
Last Update Posted : August 12, 2005
Information provided by:
Universitätsklinikum Hamburg-Eppendorf

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

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Metyrapone Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Enrollment : 63 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo Controlled Trial of Metyrapone as Augmenting Agent in the Treatment of Major Depression
Study Start Date : May 1998
Study Completion Date : July 2001

Resource links provided by the National Library of Medicine

Drug Information available for: Metyrapone

Primary Outcome Measures :
  1. 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
  2. the course of concentrations of ACTH, cortisol, 11-deoxycortisol and DHEA.

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00125554

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

Publications of Results: Identifier: NCT00125554     History of Changes
Other Study ID Numbers: HH-PSY-ja-007
First Posted: August 1, 2005    Key Record Dates
Last Update Posted: August 12, 2005
Last Verified: July 2005

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

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