Objective:

To characterize the associations between treatment-induced changes in estradiol, serotonin, and BDNF and antidepressant response in perimenopausal women receiving TCM-Acu versus SSRIs.

Approach:

• Study Design: Single-center retrospective cohort study involving 240 perimenopausal women treated for a minimum of eight weeks.
• Statistical Analysis: Multivariable-adjusted regression (ANCOVA) was used to estimate treatment effects, accounting for baseline imbalances.
• Biomarker Assessment: Examined treatment × ΔBiomarker interaction terms to assess associations between treatment and biomarker changes.

Key Findings:

• TCM-Acu showed significantly greater improvement in HAMD-17 scores compared to SSRIs (adjusted β = 3.79 points, P < 0.001).
• Absolute treatment response rates were low in both groups (14.2% for TCM-Acu vs. 5.0% for SSRIs).
• TCM-Acu was associated with greater increases in serotonin (5-HT) and BDNF levels compared to SSRIs.
• Unadjusted estradiol levels did not differ significantly between the two treatment groups.
• Changes in 5-HT and BDNF were positively associated with HAMD-17 improvement.

Interpretation:

The findings suggest that TCM-Acu may have a relative advantage over SSRIs in improving depressive symptoms and increasing serotonin and BDNF levels, but both treatments had low absolute response rates.

Limitations:

• Retrospective single-center design limits generalizability.
• Baseline imbalances may affect results.
• Absence of a sham acupuncture control.
• Differential treatment durations complicate causal inference.

Conclusion:

The study indicates that TCM-Acu may be associated with greater improvements in depressive symptoms and biomarker changes compared to SSRIs, but further prospective studies are needed to confirm these findings.