A major research study led by St Patrick’s Mental Health Services (SPMHS) and Trinity College Dublin and has been published in JAMA Psychiatry. The study examined the potential benefits of using the drug ketamine as an add-on treatment for people receiving inpatient care for depression.
While ketamine has been attracting attention internationally for its possible antidepressant effects, this large-scale randomised clinical trial found that repeated doses did not provide extra benefit beyond standard treatment. These findings add important clarity to ongoing discussions around new and emerging therapies for depression and underscore the importance of rigorous, evidence-based research in guiding clinical practice.
Collaborative research into treatment for depression
The KARMA-Dep 2 Trial brought together researchers from St Patrick’s Mental Health Services, Trinity College Dublin, and Queen’s University Belfast. Led by Professor Declan McLoughlin, Research Professor of Psychiatry at Trinity and Consultant Psychiatrist at St Patrick’s Mental Health Services, the trial explored whether twice-weekly ketamine infusions could enhance recovery for people hospitalised with depression when combined with usual inpatient care.
Investigating new approaches to care
Depression remains one of the leading causes of disability worldwide. While existing antidepressant medications help many people, some do not experience enough improvement, leading researchers to explore new ways to support recovery. Ketamine, when given in low doses, has been suggested as a promising option, though the evidence so far has been mixed.
Adding to international understanding
The KARMA-Dep 2 Trial aimed to test ketamine’s effects under the most rigorous research conditions. The results showed no added benefit from ketamine compared with standard care, helping to refine global understanding of its role in treating depression.
Speaking about the impact of the findings, Declan McLoughlin, Research Professor of Psychiatry at Trinity College Dublin and Consultant Psychiatrist at St Patrick’s Mental Health Services, said:
“Our initial hypothesis was that repeated ketamine infusions for people hospitalised with depression would improve mood outcomes. However, we found this not to be the case. Under rigorous clinical trial conditions, adjunctive ketamine provided no additional benefit to routine inpatient care during the initial treatment phase or the six-month follow-up period. Previous estimates of ketamine’s antidepressant efficacy may have been overstated, highlighting the need for recalibrated expectations in clinical practice.”
Lead author of the study, Dr Ana Jelovac, Trinity College Dublin, said:
“Our trial highlights the importance of reporting the success, or lack thereof, of blinding in clinical trials. Especially in clinical trials of therapies where maintaining the blind is difficult, e.g. ketamine, psychedelics, brain stimulation therapies. Such problems can lead to enhanced placebo effects and skewed trial results that can over-inflate real treatment effects.”.
Contributing to future research
Publication of this study reflects the commitment of St Patrick’s Mental Health Services to advancing evidence-based mental healthcare and contributing to international psychiatric research. The findings will inform future studies and support continued efforts to improve outcomes for people experiencing depression.
