What question did this study set out to answer?

This study aimed to assess the effect of comorbid generalized anxiety disorder (GAD) on treatment outcomes of rTMS/iTBS in patients with major depressive disorder (MDD).

February 2, 2026Open Access

Impact of Comorbid Generalized Anxiety Disorder on rTMS/iTBS Clinical Outcomes in Major Depression: A Multicenter Registry-Based Observational Study

Puntos clave

This study aimed to assess the effect of comorbid generalized anxiety disorder (GAD) on treatment outcomes of rTMS/iTBS in patients with major depressive disorder (MDD).
Conducted a retrospective observational study using registry data from 108 MDD patients, divided into groups with and without GAD.
Analyzed treatment outcomes using the Montgomery–Åsberg Depression Rating Scale and Hamilton Depression Rating Scale.
Applied logistic and linear regression models adjusted for demographic factors and baseline severity.
Performed sensitivity analyses based on stimulation protocol and benzodiazepine use.
No significant difference in baseline severity between the two groups.
MADRS score reduction was slightly lower in the GAD group (48.3% vs. 52.7%), but not statistically significant.
Response and remission rates were comparable between both groups.
Neither concomitant medication use nor stimulation protocol showed significant associations with treatment outcomes.

Resumen

Background: Major depressive disorder (MDD) is often accompanied by generalized anxiety disorder (GAD), a comorbidity linked to greater illness burden and potentially poorer outcomes. Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are established treatments for MDD, yet the impact of comorbid GAD and concomitant medications remains unclear. This study aimed to compare rTMS/iTBS treatment outcomes between patients with MDD with and without comorbid GAD, and to examine the association between concomitant psychotropic medication use, stimulation protocol, and treatment response in a real-world clinical setting. Methods: We conducted a retrospective observational analysis using registry data from 108 patients (MDD + GAD: n = 36; MDD only: n = 72). Patients received either Left-iTBS or Right-rTMS. Baseline severity, percentage change in Montgomery–Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAMD-17) scores, response, and remission were assessed. Logistic and linear regression models adjusted for age, sex, and baseline severity were applied. Sensitivity analyses stratified by stimulation protocol and benzodiazepine (BDZ) use were performed. Results: Baseline severity did not differ between groups. MADRS reduction was numerically lower in the comorbid GAD group (48.3% vs. 52.7%, p = 0.09), whereas HAMD-17 reduction was comparable. Response and remission rates did not differ significantly. Medication use and stimulation protocol did not show statistically significant independent associations with outcomes. Sensitivity analyses confirmed equivalent outcomes between Left-iTBS and Right-rTMS. BDZ users showed a non-significant trend toward lower MADRS improvement and remission. Conclusions: rTMS/iTBS produced substantial clinical improvement and was well tolerated in both patients with MDD and those with MDD comorbid with GAD. Although comorbid anxiety showed a modest tendency to attenuate MADRS score reduction, overall response and remission rates were comparable between groups. Neither concomitant medications nor stimulation protocol significantly affected treatment outcomes, while the potential influence of BDZ exposure warrants further investigation.

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