Efficacy of repetitive transcranial magnetic stimulation for mild postpartum depression and its association with changes in plasma neuropeptide levels: a prospective, non-randomized controlled study.

OBJECTIVE

To evaluate the efficacy of high-frequency rTMS targeting the left DLPFC in mild postpartum depression (PPD) and its association with plasma neuropeptide levels (BDNF, NPY, SP, and oxytocin).

METHODS

In this prospective, non-randomized controlled study, 120 women with mild PPD received rTMS plus standard care (n = 60; 10 Hz, left DLPFC, 20 sessions over 4 weeks) or standard care alone (n = 60). HAMD-17 and EPDS scores and plasma BDNF, NPY, SP, and OXT (ELISA) were assessed at baseline and weeks 2, 4, and 8. Longitudinal between-group effects were analyzed using linear mixed-effects models, with neuropeptide comparisons corrected by the Benjamini-Hochberg false discovery rate (FDR).

RESULTS

Baseline characteristics were largely comparable, except for breastfeeding pattern (P = 0.012). At week 4, the rTMS group had lower HAMD-17 (6.55 vs. 9.30; P < 0.001) and EPDS scores (6.15 vs. 9.27; P < 0.001), with higher response (58.3% vs. 3.3%) and remission rates (71.7% vs. 15.0%; both P < 0.001), although controls also improved. rTMS-treated patients showed elevated plasma BDNF (27.30 vs. 20.27 ng/mL), NPY (114.60 vs. 98.63 pg/mL), and OXT (181.25 vs. 163.00 pg/mL) and reduced SP (52.69 vs. 62.27 pg/mL) at week 4 (all P ≤ 0.009; all surviving FDR correction). The OXT difference persisted after adjustment for baseline OXT and breastfeeding. Within-group neuropeptide changes did not correlate with individual symptom change. Benefits persisted at 8 weeks; adverse events were mild and self-limiting.

CONCLUSIONS

In this non-randomized study without a sham control, rTMS added to standard care was associated with greater improvement in mild PPD than standard care alone, sustained through 8 weeks. The concurrent modulation of BDNF, NPY, SP, and OXT represents an exploratory association rather than an established mechanism. These preliminary findings require confirmation in multicenter, randomized, sham-controlled trials.