Review finds no reliable way to predict who responds to ketamine, ECT or TMS for depression

The question

Can doctors predict in advance which people with treatment-resistant depression will respond to ketamine or esketamine, electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS)?

What they did

The authors searched PubMed, Embase and Google Scholar for English-language, peer-reviewed studies that looked at predictors of response in adults with treatment-resistant depression. They followed PRISMA 2020, a standard reporting method for systematic reviews. From 408 studies screened, 42 were included: 23 on ketamine or esketamine, 14 on rTMS and 11 on ECT. Predictors were sorted into clinical, biological and brain-imaging categories.

What they found

Predictors fell into three groups: clinical features such as symptom profile and how long the illness had lasted; biological markers such as IL-6, CRP and BDNF (markers linked to inflammation and brain cell signalling); and imaging findings such as cingulate cortex activity and brain network connectivity. Inflammation markers and fronto-limbic brain network findings came up across all three treatments, but results were inconsistent between studies. The authors concluded the evidence is weak and that no predictor is currently useful in the clinic. No consistent predictors emerged for choosing one treatment over another.

The fine print

The review does not report a total number of participants, and the individual studies were small and used different methods, which makes them hard to compare. No pooled statistical analysis was reported. Non-English studies were excluded, which may have left out relevant work. This summary is based on the abstract only.

What it means

At present there is no reliable blood test, brain scan or clinical feature that tells doctors in advance who will benefit from ketamine, ECT or rTMS for hard-to-treat depression. Larger and more directly comparative studies are needed.

Evidence grade: Low. A systematic review that summarizes mostly small studies with differing methods and no pooled statistical analysis, so the conclusions are descriptive rather than definitive.

This summary is based on the study’s published abstract.