No significant change in salivary cortisol levels by repetitive transcranial magnetic stimulation treatment in patients with treatment-resistant depression

Background Although repetitive transcranial magnetic stimulation (rTMS) is effective for treatment-resistant depression (TRD), its impact on the hypothalamic-pituitary-adrenal (HPA) axis remains poorly understood. We investigated the relationship between rTMS-induced clinical changes and salivary cortisol levels in patients with TRD. Methods: Thirty-five patients with TRD received 6-week high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. Depressive symptoms (the 24-item Hamilton Depression Rating Scale; HAM-D24) and salivary cortisol levels (measured at 2:00 PM) were assessed at baseline and post-treatment. A mixed-model repeated measures (MMRM) analysis was performed to adjust for smoking, body mass index, and imipramine-equivalent antidepressant dosage. Results rTMS significantly improved HAM-D24 scores (p < 0.01). However, no significant overall change in salivary cortisol was observed (0.15 ± 0.06 to 0.18 ± 0.11 μg/dl, p = 0.13). MMRM analysis confirmed no significant treatment effect on cortisol after adjusting for confounders (p = 0.13). Subgroup analysis revealed a significant cortisol increase only in patients with severe depression (HAM-D24 ≧ 30, p = 0.02), though the sample size was small. Conclusions While our results did not show a significant change in salivary cortisol levels following rTMS, these findings should be interpreted with caution due to several methodological limitations. Further studies using a sham rTMS procedure with larger sample sizes and multiple sampling points are warranted.