Neurophysiological and neuroimaging markers of repetitive transcranial stimulation treatment response in major depressive disorder: a systematic review and meta-analysis of predictive modeling studies

Predicting repetitive transcranial magnetic stimulation (rTMS) treatment outcomes in major depressive disorder (MDD) could reduce the financial and psychological risks of treatment failure. We systematically reviewed and meta-analyzed studies that leveraged neurophysiological and neuroimaging markers to predict rTMS response in MDD. Five databases were searched from inception to May 25, 2023. The primary meta-analytic outcome was predictive accuracy pooled from classification models. Regression models were summarized qualitatively. A promising marker was identified if it showed a sensitivity and specificity of 80% or higher in at least two independent studies. Searching yielded 36 studies. Twenty-two classification modeling studies produced an estimated area under the summary receiver operator curve of 0.87 (95% CI = 0.83 to 0.92), with 86.8% sensitivity (95% CI = 80.6 to 91.2%) and 81.9% specificity (95% CI = 76.1 to 86.4%). Frontal theta cordance measured by electroencephalography is closest to proof of concept. Predicting rTMS response using neurophysiological and neuroimaging markers is promising for clinical decision-making. However, replications by different research groups are needed to establish rigorous markers.