Effectiveness of intermittent theta-burst stimulation for major depressive disorder with and without neurodevelopmental comorbidities: A real-world retrospective observational study.

BACKGROUND

Intermittent theta-burst stimulation (iTBS) is an established neuromodulation treatment for major depressive disorder (MDD). However, its clinical effectiveness in patients with comorbid neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), remains insufficiently understood despite their high prevalence and distinct neurocognitive and sensory profiles.

METHODS

This retrospective cohort study analyzed real-world registry data from three TMS clinics in Tokyo. All participants met DSM-5 criteria for MDD, and ASD/ADHD diagnoses were confirmed by board-certified psychiatrists. Patients received left-DLPFC iTBS using the Beam F3 method. Primary outcomes included percentage changes in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAMD-17) scores, response and remission rates, and adverse events. Group differences were examined using t-tests, ANOVA, chi-square tests, and multivariable regression adjusting for demographic and treatment-related covariates.

RESULTS

Patients without neurodevelopmental comorbidities demonstrated significantly greater symptom improvement and higher remission rates than those with ASD/ADHD (TD vs. neurodiverse). These differences persisted after covariate adjustment, indicating an independent effect of neurodevelopmental status. Baseline MADRS severity consistently predicted poorer outcomes across all models. Sensitivity analyses confirmed attenuated improvement in each neurodiverse subgroup. Findings for the ASD/ADHD subgroup were exploratory. Neurodiverse patients also reported higher rates of stimulation-site pain, although no serious adverse events occurred.

CONCLUSIONS

iTBS is effective for MDD in routine clinical practice; however, its therapeutic impact appears moderately reduced in patients with ASD and/or ADHD. These findings underscore the need for individualized neuromodulation strategies and further investigation into neurobiological and sensory factors contributing to treatment heterogeneity.