GENetic and clinical Predictors Of treatment response in Depression: the GenPod randomised trial protocol

Laura Thomas¹ , Jean Mulligan¹ , Victoria Mason² , Debbie Tallon¹ , Nicola Wiles¹ , Philip Cowen³ , David Nutt¹ , Michael O'Donovan⁴ , Deborah Sharp¹ , Tim Peters¹ and Glyn Lewis¹

¹Department of Community Based Medicine, University of Bristol, 25 Belgrave Road, Bristol, BS8 2AA, UK

²Psychology and Health Sciences, University of Worcester, Henwick Grove, Worcester, WR2 6AJ, UK

³University Department of Psychiatry, Neurosciences Building, Warneford, Hospital, Oxford, OX3 7JX, UK

⁴Department of Psychological Medicine, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK

author email corresponding author email

Trials 2008, 9:29doi:10.1186/1745-6215-9-29


Published:	22 May 2008

Abstract

Background

The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin (Selective Serotonin Reuptake Inhibitors – SSRIs) and noradrenaline (Noradrenaline Reuptake Inhibitors – NaRIs) into the presynaptic terminal. There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action. Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs, there are patients who respond to one class of compounds and not another. This suggests that treatment response could be predicted by genetic and/or clinical characteristics.

Firstly, this study aims to investigate the influence of a polymorphism (SLC6A4) in the 5HT transporter in altering response to SSRI medication. Secondly, the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs.

Methods/design

The GenPod trial is a multi-centre randomised controlled trial. GPs referred patients aged between 18–74 years presenting with a new episode of depression, who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse. Patients were interviewed to ascertain their suitability for the study. Eligible participants (with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory (BDI) score > 14) were randomised to receive one of two antidepressant treatments, either the SSRI Citalopram or the NaRI Reboxetine, stratified according to severity. The final number randomised to the trial was 601. Follow-up assessments took place at 2, 6 and 12 weeks following randomisation. Primary outcome was measured at 6 weeks by the BDI. Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments.

Discussion

The results of the trial will provide information about targeting antidepressant treatment for individual patients; in turn this may increase prescribing efficacy, thereby speeding recovery and reducing the cost to the NHS. It will also help to understand the different roles that noradrenaline and serotonin might play in the biology of depression.

The trial is expected to report in the autumn of 2008.

Trial Registration

ISRCTN 31345163