Ketamine as an adjunctive therapy for major depression- a randomised controlled trial

According to the World Health Organisation, depression is now the leading cause of disability worldwide.  Depression can be a chronic disorder, with 5-9 episodes per lifetime, and 30% of sufferers don’t respond to adequate trials of antidepressant drugs and/or talking therapies.  This creates a great societal as well as personal burden.  Moreover, when these treatments do work they can take many weeks to exert their effect.

There is thus a need for better and more rapid-acting treatments for depression. One possibility is the anaesthetic ketamine, which can be abused as a “party drug” because of its dissociative effects, such as feeling like you’re floating or even out of your body.  However, a recent landmark finding is that single low-dose slow ketamine infusions have remarkably strong and rapid antidepressant effects. Fortunately, using ketamine with proper supervision is safe and effective.  Ketamine works differently to currently used antidepressants and there is evidence that it may change brain cell pathways and connections, a process called neuroplasticity. However, little has been reported about using repeated ketamine as an “add-on” or adjunctive therapy in real-world practice.   

In this study, people hospitalised with severe depression will be randomised to receive either ketamine or the placebo drug midazolam once weekly for four weeks. This will be in addition to their regular care to assess what happens in routine clinical work. Neither patients nor researchers will know what treatment is being given and we will follow-up patients for another six months to assess long-term effects. We will also investigate the safety and comfort of this treatment, as well as possible cost and quality-of-life benefits, using a number of scientific questionnaires. Investigating whether ketamine can improve recovery from depression has the potential to improve the quality of life of the 6,000 people in Ireland hospitalised each year with depression.

Award Date
07 March 2019
Award Value
Principal Investigator
Professor Declan McLoughlin
Host Institution
Trinity College Dublin