Protocol for the THREAD (THREshold for AntiDepressants) study: a randomised controlled trial to determine the clinical and cost-effectiveness of antidepressants plus supportive care, versus supportive care alone, for mild to moderate depression in UK general practice

BACKGROUND: Depression guidelines in the UK recommended a policy of watchful waiting for mild depression due to a lack of evidence for the effectiveness of antidepressant treatment for mild cases. However there has been relatively little research carried out in primary care to help establish the severity threshold at which antidepressant treatment is effective and cost-effective. METHODS/DESIGN: The THREAD (THREshold for AntiDepressants) study is a multi-centre randomised controlled trial designed to determine the clinical and cost effectiveness of a selective serotonin reuptake inhibitor (SSRI) plus general practitioner (GP) supportive care, versus supportive care alone, for mild to moderate depression in primary care. The aim is to recruit 300 patients from three centres (Southampton, London and Liverpool). Depressive symptoms will be assessed at baseline, 12 weeks and 26 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS). Two severity sub-groups of patients will be recruited, with HDRS scores of 12–15, and 16–19. Possible predictors of response will be explored including life events and difficulties and alcohol consumption. Analysis of covariance, controlling for baseline value, severity group and centre will be used to estimate the overall treatment effectiveness (difference in HDRS score) at final follow up. The primary analysis will be by 'intention to treat' using double sided tests. The interaction between severity sub-group and treatment will be tested, and if appropriate, effects within separate severity sub-groups estimated. The economic analysis will compare the two treatment groups in terms of mean costs and cost-effectiveness. DISCUSSION: The results of this study will give GPs important information to help them determine the severity of depression at which antidepressant treatment is likely to be cost-effective.