What is it about?
This study investigates whether low-grade inflammation influences the rapid antidepressant and antisuicidal effects of low-dose ketamine in patients with treatment-resistant depression (TRD). Using pooled data from three clinical trials, treatment outcomes were compared between patients with and without elevated inflammatory markers during the first three days following ketamine infusion.
Why is it important?
Although ketamine has been widely studied for its rapid effects in TRD and suicidal ideation, patient responses remain highly variable. Low-grade inflammation has been linked to poorer outcomes with conventional antidepressants and may reflect a biologically distinct subtype of depression. Clarifying whether inflammatory status moderates ketamine’s effects is important for interpreting clinical trial results and for advancing research on biological heterogeneity in depression.
Main findings
- A significant antidepressant effect of ketamine was observed only in patients without low-grade inflammation.
- In patients with low-grade inflammation, ketamine did not demonstrate a clear advantage over placebo in reducing overall depressive symptoms.
- Antisuicidal effects were observed regardless of inflammatory status, although they were more pronounced in patients without inflammation.
- Patients with low-grade inflammation showed a higher placebo response, which may have reduced the apparent antidepressant effect of ketamine.
- The proportion of patients with low-grade inflammation in this sample was consistent with prior epidemiological estimates.
What do the authors argue?
The authors suggest that low-grade inflammation may limit the observable antidepressant effects of ketamine in treatment-resistant depression, potentially due to an enhanced placebo response rather than an absence of biological activity. They also argue that ketamine’s antisuicidal effects may be partly independent of its antidepressant effects, highlighting the complexity of underlying mechanisms and the need for further inflammation-stratified clinical trials.
Team Member Spotlight
You can find the paper here.