Efficacy of combined low-frequency rTMS and cognitive behavioral therapy for unmedicated panic disorder: A randomized...

Cognitive behavioral therapy (CBT) is a first-line intervention for panic disorder (PD), yet a subset of patients exhibits suboptimal response. This randomized controlled trial investigated whether low-frequency repetitive transcranial magnetic stimulation (rTMS) augments the efficacy of CBT in unmedicated PD patients.

Fifty patients with PD were randomly assigned to receive either active or sham rTMS combined with standardized CBT. Outcomes were assessed using the Panic Disorder Severity Scale (PDSS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD-17), Clinical Global Impression-Severity (CGI-S), Symptom Checklist-90 (SCL-90), and Personal and Social Performance scale (PSP). Bayesian linear mixed-effects model (LMM) was employed to analyze changes in clinical scores over time, accounting for repeated measures and baseline severity. Sensitivity analysis was also performed to evaluate the robustness of the findings.

LMM analysis revealed a significant group × time interaction for both PDSS and HAMA scores. The active rTMS group showed significantly greater reduction in panic and anxiety symptoms compared to the sham group from week 2 onward. At the 12-week endpoint, both groups demonstrated significant improvements in overall psychopathological symptoms (SCL-90), depressive symptoms (HAMD-17), illness severity (CGI-S), and psychosocial functioning (PSP). However, the active rTMS group demonstrated significantly greater improvement in PSP scores compared to the sham control group, while no superior improvement was observed in SCL-90, CGI-S, or HAMD-17 scores. Both treatments were well tolerated.

Active rTMS significantly accelerated and enhanced early anxiety and panic symptom reduction when combined with CBT, demonstrating its potential as an effective adjunctive strategy in the initial phase of treatment. The combination was safe and feasible, supporting further investigation into optimized sequencing and long-term outcomes in PD management.