IMPase in treatment-resistant depression
Research type
Research Study
Full title
Does the IMPase inhibitor, ebselen, affect emotional processing and brain myo-inositol in treatment-resistant depression?
IRAS ID
276211
Contact name
Philip J Cowen
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 11 months, 28 days
Research summary
Depression is a mental health condition that is associated with a substantial burden of suffering for both patients and their families. Most patients with depression do well with first line treatments such as psychotherapy or antidepressant medication but for those who are not helped sufficiently there are few effective and acceptable next step treatments. For patients who do not respond to antidepressants (and have so-called ‘treatment-resistant depression’), a drug called lithium is an effective ‘add-on’ therapy. However, lithium has some problematic side effects and requires blood test monitoring which reduces its usefulness. Greater knowledge of how lithium works in treatment resistant depression would help in the development in new medicines with an improved safety profile.
Our team at Oxford has been studying a drug called ebselen, which has as the ability to block an enzyme called IMPase. Animal experimental research has suggested that blockade of IMPase might be the basis of lithium’s antidepressant action. Ebselen was originally developed for the treatment of stroke and appears safe, with very few reported side-effects. It is therefore a useful way of finding out if IMPase inhibition could be a potential antidepressant mechanism. To take a first step in finding out if this could be the case we propose to use an ‘experimental medicine’ approach where we will examine the effects of a brief period (seven days) of ‘add-on’ ebselen treatment in patients with resistant depression to see if ebselen produces changes in emotional responses consistent with a potential clinical antidepressant effect. We will also seek to confirm ebselen’s mode of action on IMPase by measuring changes in a brain chemical called inositol, using a magnetic imaging method. Positive results from this study could lead to the development of selective IMPase inhibitors for the treatment of depression.
The study is funded by Medical Research Council.
REC name
South Central - Oxford B Research Ethics Committee
REC reference
20/SC/0151
Date of REC Opinion
4 Jun 2020
REC opinion
Further Information Favourable Opinion