Is rTMS effective for anxiety symptoms in major depressive disorder? An efficacy analysis comparing left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS protocols

Background: Anxiety symptoms are common in major depressive disorder. Whilst therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is well-established, minimal research has investigated rTMS's efficacy in treating anxiety symptoms in depression. Methods: This study investigates the effectiveness of rTMS in treating anxiety symptoms in depression, specifically the relative efficacy of the three rTMS protocols commonly used in clinical practice: left-sided high-frequency, right-sided low-frequency and sequential bilateral rTMS. Antidepressant efficacy of each rTMS protocol is also investigated. Treatment data for 697 patients were pooled from three studies across five sites. Changes in Beck's Anxiety Inventory (BAI) and the Hamilton Depression Rating Scale over 4-week rTMS courses were analysed using latent growth curve modelling. Results: All rTMS protocols were effective in treating anxiety symptoms (mean BAI reduction, 8.13 points; p < 0.001) and depressive symptoms. Near therapeutic equivalence was seen across the three protocols. Improvement in depressive severity positively correlated with improvement in anxiety. Both high- and low-baseline anxiety scores showed overall symptom reduction. Conclusions: This study addresses the clinical knowledge gap pertaining to rTMS's therapeutic efficacy in treating anxiety symptoms in depression and the relative efficacy of three commonly used stimulation protocols. Our findings suggest therapeutic equivalence across left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS approaches.