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

BMC Psychiatry

Study Protocol

Najma Siddiqi¹  Peter M Haddad²  Ian M Anderson²  Simon HS Pearce³  Allan O House⁴  Stuart Watson⁵  Peter Gallagher⁵  I Nicol Ferrier⁵  Heinz CR Grunze⁵  Adrian J Lloyd⁵  R Hamish McAllister-Williams⁶  Tom Hughes⁷  Fiona H Winter⁸  June Wainright⁸  Jane Barnes⁹  Chris Speed⁹  I Nick Steen⁹  Elaine MM McColl⁹  Eleanor Smith^1,10  Baxi Sinha^1,11 

[1] Bradford District NHS Care Trust, Bradford, UK;Greater Manchester West Mental Health NHS Foundation Trust and Neuroscience and Psychiatry Unit, Manchester University, Manchester, UK;Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK;Institute of Health Sciences, University of Leeds, Leeds, UK;Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK;Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK;Academic Psychiatry, Wolfson Research Centre, Campus for Ageing and Vitality, NE4 5PL, Newcastle upon Tyne, UK;Leeds and York Partnership NHS Foundation Trust, Leeds, UK;Mental Health Research Network, North East Hub service user and carer group, Newcastle, UK;Newcastle Clinical Trials Unit, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK;Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK;Tees, Esk and Wear Valleys NHS Foundation Trust, Edward Pease Way, Darlington, County Durham, UK;

关键词: Antidepressive agents;    Cortisol;    Depressive disorder;    Metyrapone;    Antiglucocorticoid treatment;    Treatment refractory depression;   

DOI  :  10.1186/1471-244X-13-205

 received in 2013-06-22, accepted in 2013-07-25,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundSome 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/designPatients 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.DiscussionStrengths 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 registrationCurrent Controlled Trials: ISRCTN45338259; EudraCT Number: 2009-015165-31.

【 授权许可】

CC BY   
© McAllister-Williams et al.; licensee BioMed Central Ltd. 2013