Antiglucocorticoid Augmentation of antiDepressants in Depression

Summary

Depression is one of the most common mental health problems, with at least one in six adults suffering from this at some time in their life. It can become long-lasting and frequently recurs. Depression has a large negative impact on quality of life of patients and their carers and it has also been shown to be one of the leading causes of working age adults receiving disability payments in the UK. The need for improved treatment has been recognised by the Department of Health and others. Improvements in drug treatments are therefore required. There has been recent increased understanding of some of the causes of the frequent lack of complete response seen with antidepressants. The stress hormone, cortisol, is often elevated or poorly controlled in depression and there is laboratory and clinical research to show that this hormonal change reduces the benefits from antidepressants with associated poor outcome and memory problems. Recently it has been shown in small studies that giving treatments that reduce cortisol or block its harmful effects for between 1 and 3 weeks overcome these negative consequences. Our group is particularly interested and experienced in this topic. The investigators plan to study a drug that decreases cortisol levels in people who have not recovered with standard antidepressants so that the investigators can find out the usefulness of this treatment (compared with placebo (dummy tablet)) in day to day life as well as checking closely for side-effects (the initial studies have shown that the particular drug the investigators wish to study (metyrapone) has few side effects). The investigators will also measure cortisol and see if its level can tell us which people do best with this treatment. The investigators will carry out this study in 3 centres across the UK. The investigators will carry out some additional tests of specific sorts of memory and decision making and also do this while scanning the brain (in a painless test). The results of these tests, along with tests of brain wave patterns, should help us understand more fully how this new treatment is working and who responds best to it. The study will help us find out if this drug should be used more widely for people not responding to standard treatments and will also lead on to the development of other new treatments with an anti-cortisol effect to help tackle the major problem of poor outcome from depression.

Conditions

• Depression

Interventions

DRUG

Metyrapone

500 milligrams to be taken twice a day orally

DRUG

placebo

a matched placebo will be administered to patients to take twice a day for 3 weeks

Sponsors & Collaborators

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• Jane Barnes

  lead OTHER

Principal Investigators

• Ian N Ferrier, MRCPsych · Newcastle University

• Richard H McAllister-Williams, FRCP · Newcastle University

• Stuart Watson, MRCPsych · Newcastle University

• Ian M Anderson, FRCPsych · Manchester University

• Allan O House, MRCPsych · Leeds University

• Elaine M McColl, PhD · Newcastle University

• Ian N Steen, PhD · Newcastle University

• Heinz CR Grunze, BoardCertPsy · Newcastle University

• Peter M Haddad, MRCPsych · Manchester University

• Thomas A Hughes, MRCPsych · Leeds Partnerships NHS Foundation Trust

• Adrian Lloyd, MRCPsych · Northumberland, Tyne and Wear NHS Trust

• Andrew M Blamire, BSc, PhD · Newcastle University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2011-02-28

Primary Completion

2013-02-28

Completion

2013-06-30

Countries

• United Kingdom

Study Locations