Ketamine for relapse prevention in recurrent depressive disorder: a randomised controlled pilot trial (The KINDRED Trial)

Depression is projected to become the second greatest cause of disability worldwide by 2020. It can be a chronic disorder, with 5-9 episodes of depression per lifetime. The first six months following successful antidepressant treatment represents the highest risk period for relapse, with 40-60% relapse rates in persons with difficult-to-treat resistant depression. Continuing antidepressant treatment is recognised as important in reducing risk of relapse. However, many people still experience recurrent episodes despite intensive treatments, including medications and talking therapies. There is therefore a need for better relapse prevention strategies in recurrent depressive disorder. This study will investigate whether a new antidepressant called ketamine may be of use in this key clinical problem. Ketamine has been used as a general anaesthetic for many years but, more recently; it has been found to have a remarkably strong and rapid antidepressant effect. Ketamine works differently to currently used antidepressants and exactly how it causes its antidepressant effect is not known. There is evidence that it may change brain cell pathways and connections, a process called neuroplasticity. In this study, people who have recurrent depressive disorder (i.e. three or more episodes in the previous two years) and who have just become well again will be randomised to receive either ketamine or the placebo drug midazolam once every two weeks for eight weeks. This is a high-risk group for relapse and most relapse will occur in the first six months. We will therefore perform follow-up mood assessments over six months to see if ketamine helps prevent relapse of depression. We will also investigate the safety and comfort of this treatment using a number of scientific questionnaires. Investigating whether ketamine can help prevent relapse has the potential to improve the quality of life of some 300,000 people in Ireland who suffer from depression.


Award Date
30 June 2016
Award Value
Principal Investigator
Professor Declan McLoughlin
Host Institution
Trinity College Dublin
MRCG-HRB Joint Funding Scheme