Study protocol for the randomised controlled trial: antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study)

Autor: I. Nicol Ferrier, June Wainright, I Nick Steen, Heinz Grunze, Jane Barnes, Baxi Sinha, Najma Siddiqi, Adrian J. Lloyd, Allan House, Eleanor Smith, Peter M. Haddad, Stuart Watson, Chris Speed, Simon H. S. Pearce, Elaine McColl, Fiona H Winter, Tom Hughes, Ian M. Anderson, Peter Gallagher, R. Hamish McAllister-Williams
Rok vydání: 2013
Předmět:
Oncology
Male
Placebo-controlled study
Pilot Projects
Cortisol
law.invention
chemistry.chemical_compound
Depressive Disorder
Treatment-Resistant
Study Protocol
0302 clinical medicine
Randomized controlled trial
Clinical Protocols
law
Medicine
10. No inequality
Depression (differential diagnoses)
Antiglucocorticoid
Middle Aged
Antidepressive Agents
3. Good health
Psychiatry and Mental health
Research Design
Drug Therapy
Combination
Female
Selective Serotonin Reuptake Inhibitors
medicine.drug
Adult
medicine.medical_specialty
Treatment refractory depression
Adolescent
Serotonergic
03 medical and health sciences
Young Adult
Pharmacotherapy
Internal medicine
Humans
Serotonin Uptake Inhibitors
Psychiatry
Aged
Depressive Disorder
Major
Metyrapone
business.industry
Depressive disorder
Antiglucocorticoid treatment
030227 psychiatry
chemistry
Quality of Life
business
030217 neurology & neurosurgery
Zdroj: BMC Psychiatry
ISSN: 1471-244X
Popis: Background Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake inhibitors to increase forebrain 5-hydroxytryptamine, while co-administration of antiglucocorticoids has the opposite effect. A Cochrane review suggests that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD and includes a pilot study of the cortisol synthesis inhibitor, metyrapone. The Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study) is a multicentre randomised placebo controlled trial of metyrapone augmentation of serotonergic antidepressants in a large population of patients with TRD in the UK National Health Service. Methods/design Patients with moderate to severe treatment refractory Major Depression aged 18 to 65 will be randomised to metyrapone 500 mg twice daily or placebo for three weeks, in addition to on-going conventional serotonergic antidepressants. The primary outcome will be improvement in Montgomery-Åsberg Depression Rating Scale score five weeks after randomisation (i.e. two weeks after trial medication discontinuation). Secondary outcomes will include the degree of persistence of treatment effect for up to 6 months, improvements in quality of life and also safety and tolerability of metyrapone. The ADD Study will also include a range of sub-studies investigating the potential mechanism of action of metyrapone. Discussion Strengths of the ADD study include broad inclusion criteria meaning that the sample will be representative of patients with TRD treated within the UK National Health Service, longer follow up, which to our knowledge is longer than any previous study of antiglucocorticoid treatments in depression, and the range of mechanistic investigations being carried out. The data set acquired will be a rich resource for a range of research questions relating to both refractory depression and the use of antiglucocorticoid treatments. Trial registration Current Controlled Trials: ISRCTN45338259; EudraCT Number: 2009-015165-31.
Databáze: OpenAIRE
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