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

Daniel Pustay, Vishal Patel, Krista Ulisse, Jourdan Aromin

Figshare 2026 DOI: 10.6084/m9.figshare.31287835 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Population Adults with treatment-resistant depression
Topics Depression Ketamine Esketamine
Keywords Electroconvulsive therapy Transcranial magnetic stimulation Depression economics Neuroimaging Meta-analysis Magnetic resonance imaging Medline Psychological intervention Clinical psychology Clinical trial Anterior cingulate cortex Brain stimulation Sample size determination Systematic review
Key findings Weak evidence exists for a few biological, clinical, and imaging predictors of response to rTMS, ECT, or esketamine, but no consistent or clinically useful predictors emerged.

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.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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