Factors for predicting response to electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) and ketamine in patients with treatment-resistant depression: a systematic review

A systematic review of 42 studies examined factors that might predict which adults with treatment-resistant depression respond to electroconvulsive therapy, repetitive transcranial magnetic stimulation, or ketamine-based treatments. Predictive factors were grouped into clinical (symptom profile, illness duration), biological (inflammatory markers such as IL-6 and CRP, and BDNF), and imaging (cingulate cortex activity and connectivity). Some inflammation markers and fronto-limbic network findings appeared across treatments, but results were inconsistent. The review found weak evidence for a few predictors, but no consistent or clinically useful factors emerged for any modality or for comparing effectiveness between treatments. Larger, comparative studies are needed.

Study at a glance

Abstract

Treatment-resistant depression (TRD) remains a complex challenge, often requiring interventions beyond standard medications. This review explores factors that may predict positive response to electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS) and ketamine-based treatments to help guide clinical decision-making. A systematic review was conducted following PRISMA 2020 guidelines. English-language, peer-reviewed studies were identified through PubMed, Embase and Google Scholar using search terms such as ‘treatment-resistant,’ ‘outcome,’ ‘prediction,’ ‘ECT,’ ‘rTMS,’ and ‘ketamine.’ Studies were included if they examined clinical, biological or imaging predictors of response in adults with TRD. Case reports, reviews, editorials and non-English articles were excluded. A total of 42 studies were selected from 408 screened. Among these, 23 focused on ketamine/esketamine, 14 on rTMS, and 11 on ECT. Predictive factors were grouped into clinical (e.g., symptom profile, illness duration), biological (e.g., IL-6, CRP, BDNF) and imaging (e.g., cingulate cortex activity, connectivity). Inflammation markers and fronto-limbic network findings appeared across treatments, though findings were inconsistent. While some predictors show promise, clinical use remains limited by methodological differences and small sample sizes. Larger studies are required to identify clinically useful predictors. Additionally, for optimal treatment decision-making, comparative studies are necessary. There is weak evidence for a select few biological, clinical and imaging factors that may predict response to rTMS, ECT or esketamine.No consistent predictors emerged for comparative effectiveness among modalities.No clinically useful factors are indicated based on available literature. There is weak evidence for a select few biological, clinical and imaging factors that may predict response to rTMS, ECT or esketamine. No consistent predictors emerged for comparative effectiveness among modalities. No clinically useful factors are indicated based on available literature.