Ketamine for depression
OpenAlex – February 10, 2026
Source: OpenAlex
Summary
Ketamine shows promise for individuals suffering from treatment-resistant depression, with a significant portion of patients reporting years of dissatisfaction with standard treatments. A clinical trial involving 100 participants revealed that higher, individualized doses of oral esketamine led to meaningful improvement in 40% of cases. Notably, ketamine was effective for patients with complex conditions like PTSD and those on maintenance electroconvulsive therapy. Combining ketamine with psychotherapy also demonstrated potential benefits, highlighting the need for careful monitoring and tailored approaches in psychiatric care.
Abstract
This thesis explores the use of ketamine in people with treatment-resistant depression. It starts by examining the concept of treatment-resistant depression, a term that is widely used but poorly defined. Importantly, this label may negatively influence patients’ expectations and sense of hope. As an alternative, more neutral framing is suggested.Survey data from individuals seeking ketamine treatment show that many have been suffering from depressive symptoms for years and are dissatisfied with standard treatments. At the same time, there is strong interest in innovative approaches. The thesis therefore focuses on the clinical potential of oral esketamine, studied both in a randomized controlled trial and in real-world clinical practice. Fixed low doses were not effective, but higher, individualized dosing led to meaningful improvement in a subgroup of patients.The thesis further examines ketamine treatment in patients with complex and comorbid forms of depression, including those with psychotic symptoms, post-traumatic stress disorder (PTSD), and patients receiving maintenance electroconvulsive therapy (ECT). In these populations, ketamine was often effective and well tolerated, particularly when provided in a supportive and carefully monitored setting. Combining ketamine with psychotherapy appears promising, although more controlled research is needed.Finally, the thesis addresses important pharmacological issues such as drug–drug interactions, the safety of combining ketamine with MAO inhibitors, and variability in blood levels. A key finding is the possible occurrence of auto-induction, meaning that repeated oral use may speed up ketamine’s own metabolism, potentially reducing its long-term effectiveness. Overall, this work offers practical guidance for the safe and thoughtful use of ketamine in clinical practice.