Promoting the Discussion of the Beneficial Effects of Ketamine to Treat Refractory Depression
Priyanka Ghosh, Omar Viswanath
Psychopharmacology Bulletin August 12, 2025 DOI: 10.64719/pb.4579 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Placebo-controlled Peer reviewed |
|---|---|
| Intervention | Ketamine infusion therapy |
| Topics | Ketamine Depression Esketamine |
| Keywords | Depression economics Refractory planetary science Keynesian economics |
| Citations | 1 |
| Key findings | Seven placebo-controlled randomized clinical trials have shown beneficial effects of ketamine infusion therapy on refractory depression, but no large-scale trials demonstrate safety or durability, and FDA approval is lacking. |
Abstract
We read a recent article published by CNN titled “Ketamine offers lifeline for people with severe depression, suicidal thoughts1” with great interest. The article traces the story of a man with a 35-year history of severe refractory depression, suicidal ideation, and recent suicide attempts who was successfully treated with ketamine as a last resort after failing dozens of other pharmacologic psychiatric medications, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants. This incredible medical success story is not isolated to this gentleman. In fact, there has been significant data, with seven placebo controlled randomized clinical trials (RCT), that have shown the beneficial effects of ketamine infusion therapy on refractory depression.2 However, ketamine therapy for refractory depression in practice is still very limited since it continues to be an off-label use of ketamine. Unfortunately, there are currently no large scale, randomized controlled clinical trials that demonstrate the safety or durability of ketamine therapy. Another limiting factor is that patient selection criteria is limited to major depressive disorder (MDD) without psychotic features with effects lasting up to 1 week, as this is the only population and timeline successfully studied. However, there is evidence that other patients and repeated dosing could be significantly beneficial but there are no clinical trials to fully support this theory. Due to the limitations of trials demonstrating the above factors, the on-label approval of ketamine for psychiatric illness has not undergone scrutiny by the FDA.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |