Comparative response patterns and tolerability of high-frequency rTMS in unipolar versus bipolar depression: a retrospective naturalistic study

Objective This retrospective naturalistic study compared response patterns and tolerability of high-frequency left-DLPFC repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) and bipolar depressive disorder (BD) under real-world clinical conditions.Materials and Methods A total of 161 patients (95 MDD, 66 BD) who completed 20 sessions of 10 Hz rTMS between 2019 and 2023 were evaluated. Diagnoses were established using the SCID-5. Symptom severity was assessed with the Hamilton Depression Rating Scale (HAM-D). Response was defined as ≥50% HAM-D reduction, remission as post-treatment HAM-D ≤ 7. Multivariate logistic regression identified independent predictors of response.Results The MDD group demonstrated a significantly higher response rate than the BD group (48.4% vs. 28.8%; p = 0.013), while remission rates were comparable (21.1% vs. 21.2%; p = 1.000). Female patients exhibited higher response rates in both groups, reaching significance in MDD (58.8% vs. 36.4%, p = 0.029). Multivariate analysis confirmed diagnosis (OR = 2.25, p = 0.025), female sex (OR = 2.35, p = 0.014), and lower baseline HAM-D scores (OR = 0.85, p = 0.018) as independent predictors of response. rTMS was well tolerated, with mild transient side effects in 36.6% of participants and only one hypomanic activation.Conclusion In this naturalistic sample, MDD showed a higher response than BD, while remission rates were comparable. Given the retrospective, completer-based design and asymmetric sampling, these findings are exploratory and should inform future controlled studies rather than current clinical practice.