Metyrapone as Additive Treatment in Major Depression

Major Depressive Disorder Clinical Trial

Official title: Double-Blind, Placebo Controlled Trial of Metyrapone as Augmenting Agent in the Treatment of Major Depression

Status Completed

Clinical Trial Summary

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

Clinical Trial 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

• NCT number: NCT00125554
• Study type: Interventional
• Source: Universitätsklinikum Hamburg-Eppendorf
• Status: Completed
• Phase: Phase 2
• Start date: May 1998
• Completion date: July 2001