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Related Experiment Video

Updated: May 8, 2026

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Published on: August 11, 2015

Metyrapone in treatment-resistant depression.

Paul David Sigalas¹, Himanshu Garg, Stuart Watson

¹Institution of Neurosciences - Academic Psychiatry, Campus for Ageing and Vitality, Westgate Road, Newcastle NE4 6BE, UK.

Therapeutic Advances in Psychopharmacology

|August 29, 2013

Summary

Metyrapone, a cortisol synthesis inhibitor, shows promise for treatment-resistant depression (TRD). Augmenting antidepressants with metyrapone significantly improved depression scores compared to placebo in a clinical trial.

Keywords:

antidepressant antiglucocorticoid depression hypothalamic–pituitary–adrenal axis metyrapone treatment resistant

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Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

Published on: August 2, 2021

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Last Updated: May 8, 2026

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Published on: August 11, 2015

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method

Published on: August 2, 2021

Area of Science:

Neuroscience
Endocrinology
Psychiatry

Background:

Depression is prevalent, with limited remission rates for first-line treatments.
Treatment-resistant depression (TRD) necessitates novel therapeutic strategies.
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation, including elevated cortisol, is implicated in depression and treatment nonresponse.

Purpose of the Study:

To review the efficacy of pharmacological agents targeting cortisol synthesis and release for depression, particularly TRD.
To detail the evidence for metyrapone, a cortisol synthesis inhibitor, as a potential antidepressant treatment.

Main Methods:

Review of studies investigating pharmacological interventions for HPA axis dysregulation in depression.
Focus on metyrapone, including a double-blind, randomized, placebo-controlled trial.

Main Results:

Metyrapone demonstrated antidepressant efficacy when used as an augmentation therapy for serotonergic antidepressants.
A 3-week augmentation with metyrapone resulted in a 50% reduction in depression scores (Montgomery-Asberg Depression Rating Scale) compared to placebo at 5 weeks.

Conclusions:

Metyrapone shows significant potential as a treatment for depression, especially TRD.
Further research is warranted to elucidate the precise mechanisms underlying metyrapone's antidepressant action.