Optimizing RTMS for Depressive Disorders: Comparative Efficacy and Insights Into Clinical Factors

Abstract Background Depressive disorders, including major depression, bipolar depression, and dysthymia, are psychiatric conditions that severely impair emotional well-being and functionality. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy in alleviating depressive and anxiety symptoms in patients with depressive disorders. Common clinical protocols include left-sided high-frequency (10 Hz), right-sided low-frequency (1 Hz), and intermittent theta-burst stimulation (iTBS). However, comparative efficacy and interactions with clinical factors remain underexplored. This study aims to examine the short-term effects of rTMS protocols in reducing depressive and anxiety symptoms in adults with depressive disorders. Aims (2) examine the influence of anxiety and depression severity during treatment and psychotropic medication use on outcomes, and to compare the extent of improvements across diagnostic categories. Method Sixty-eight adults diagnosed with major depressive disorder (MDD; n=36), dysthymia (n=25), or bipolar depression (BD; n=7) based on DSM-5 criteria were enrolled at National Taiwan University Hospital Yunlin Branch. All participants completed at least ten rTMS sessions targeting the dorsolateral prefrontal cortex with either left-sided 10 Hz, right-sided 1 Hz, or left-sided iTBS protocols. Only data from the first ten sessions were analyzed, regardless of additional treatments. Baseline demographics (age, sex, hand dominance), psychiatric diagnoses, and rTMS parameters were recorded. Psychotropic use, HAM-D17 (17-item Hamilton Depression Rating Scale) scores for depressive symptoms, and HAM-A (Hamilton Anxiety Rating Scale) scores for anxiety symptoms were assessed at baseline, after session 5, and after session 10. Multicollinearity diagnostics eliminated variables with a variance inflation factor exceeding 10. Statistical analysis employed generalized estimating equations with backward elimination, and p-values were adjusted using the Benjamini–Yekutieli correction for multiple comparisons. Results After ten sessions, significant reductions in HAM-D17 and HAM-A scores were observed across all three protocols, with no effectiveness differences among them. Patients with higher HAM-A scores throughout the treatment period showed less improvement in HAM-D17, while HAM-D17 severity did not influence HAM-A outcomes. Symptom improvement rates were similar across MDD, BD, and dysthymia despite numerical trends. Antipsychotic use correlated with higher HAM-D17 but faster improvement, while other medications had no significant effects. Among the HAM-D17 domains (core, insomnia, anxiety, and visceral symptoms), the anxiety domain showed the least improvement. Psychic and somatic domains of HAM-A showed similar degrees of improvement. Discussion & Conclusions The comparable efficacy of all rTMS protocols highlights its broad applicability in alleviating depressive and anxiety symptoms. However, the slower improvement in depressive symptoms among patients with high anxiety underscores the need for tailored interventions in this subgroup. The observed synergy between rTMS and antipsychotics warrants further investigation. Additionally, the limited improvement in the anxiety domain of HAM-D17 highlights the challenge of addressing anxiety within depressive disorders. In conclusion, rTMS demonstrates protocol-independent benefits for depression and anxiety. Further research is needed to optimize treatment for patients with anxious depression and assess long-term effects, including variations in outcomes across protocols and diagnostic groups.