Genetic clinical and ENdocrine Predictors of treatment Outcome in Depression (GENPOD)

Lead Research Organisation: University of Bristol
Department Name: Community-Based Medicine

Abstract

There are now a wide range of antidepressants used to treat depression in primary care, but the two main types influence the neurotransmitters serotonin (5HT) or noradrenaline. We plan to investigate whether there are genetic, clinical or hormonal predictors of response to these two main types of antidepressant. We plan to carry out a clinical trial that will randomise people with depression to either of the two antidepressants. The antidepressants are equally effective overall, but it seems that some patients get better on one type and some on the other. If we can find out what predicts response it will help to target treatment and also understand more about how these tablets work. It might also help to provide a classification of different types of depression.

Technical Summary

We propose to carry out a randomised controlled trial in which subjects with depression will be randomly allocated to either reboxetine, a noradrenaline reuptake inhibitor (NaRI) or paroxetine, a serotonin reuptake inhibitor (SSRI). Outcome will be measured at 6 weeks and 12 weeks with the Beck Depression Inventory. Recruitment will occur in primary care. Measurements will be made at baseline in order to provide data on possible predictors of response to either reboxetine or paroxetine. The predictors we will examine are: genetic polymorphism at the 5HT transporter, clinical severity of depression, and a measure of hypothalamopituitary dysfunction.

Publications

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publication icon
Foo JC (2019) Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy. in American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics

 
Description Health Technology Assessment
Amount £900,000 (GBP)
Funding ID 03/45/07 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 06/2008 
End 03/2011
 
Description NIHR HTA
Amount £1,260,000 (GBP)
Funding ID 06/404/02 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2008 
End 04/2014
 
Description NIHR Programmes for Applied Research
Amount £2,000,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 06/2012 
End 05/2017
 
Description GENDEP 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution This study and mine used very similar methods allowing joint use of the data for genetic analysis.
Collaborator Contribution They have contributed data and also led the analysis on one paper.
Impact Publications that are included
Start Year 2011
 
Description Psychiatric Genetics Consortium 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution Via links with IOP have contributed to the PGC
Collaborator Contribution They coordinate large GWAS studies on psychiatric disorders
Impact Publication as listed
Start Year 2012
 
Title GENPOD 
Description This study was a stratified medicine design to refine the indications for existing antidepressants 
Type Therapeutic Intervention - Drug
Current Stage Of Development Wide-scale adoption
Development Status Under active development/distribution
Clinical Trial? Yes
Impact We could not identify factors that refined the indication for the antidepressants 
URL http://en.wikipedia.org/wiki/Citalopram
 
Description Lectures and presentations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Lectures to psychiatrists and other health professionals

None at present
Year(s) Of Engagement Activity 2006,2007,2008,2009
 
Description Psychiatric trainees in Southmead hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Health professionals
Results and Impact 40 people attended the talk - part of the postgraduate education of clinicians.

None noted.
Year(s) Of Engagement Activity 2009
 
Description Sheffield clinical presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact 30 people attended.

None
Year(s) Of Engagement Activity 2009