Background: Women are disproportionately affected by major depressive disorder (MDD). Widely used hormonal contraceptives are linked to depression and altered brain function, yet their unstudied impact on EEG-biomarkers of antidepressant response may confound efforts to develop biomarkers for women.
Methods: In 60 unmedicated premenopausal women with MDD: non-users (n = 25), combined oral contraceptive users (COC, n = 19), and progestin-only contraceptive users (POC, n = 16), we assess five EEG-biomarkers before eight weeks of 10-20 mg escitalopram: Alpha peak frequency (APF), Vigilance level, Loudness-Dependence of Auditory Evoked Potentials (LDAEP), frontal alpha asymmetry (FAA), and theta activity at the anterior cingulate cortex (tACC). Analyses include age-adjusted ANCOVAs, hierarchical logistic regression, and repeated LASSO-regressions to evaluate the effects of hormonal contraceptives on EEG-biomarkers and treatment response.
Results: No differences between contraceptive groups are found in EEG-biomarkers (ω²<0.03, p > 0.15). Adding contraceptive groups improves EEG-based predictions for all biomarkers (p < 0.044). While hierarchical regressions show no significant EEG-biomarker contraceptive-group interactions, LASSO-regressions select contraceptive status in interaction with APF and tACC in models that best predict treatment outcome. Disregarding EEG, hormonal contraceptive use is associated with treatment response (p = 0.01). COC-users exhibit lower response rates than non-users (24% vs 71%, OR = 0.14 [0.03, 0.65], p = 0.012). POC-users have a 44% response rate (p = 0.140).
Conclusions: Although hormonal contraceptive use is not associated with EEG-biomarkers in unmedicated depressed women, they may modulate links between specific EEG-biomarkers and antidepressant response. However, contraceptive use, specifically COC, is associated with worse treatment outcomes and may be critical to developing biomarkers, including EEG-based, to guide treatment in women with MDD.
Women commonly use hormonal contraceptives, which may alter brain activity in ways that might affect how antidepressants work. We measured brain waves (EEG) in 60 women with depression before they started antidepressant treatment. The women either used combined oral contraceptives, progestin-only contraceptives, or no hormonal contraceptives. We examined five EEG-biomarkers associated with antidepressant treatment response. We found that hormonal contraceptives did not directly alter these brain wave patterns. However, women using combined oral contraceptives responded poorly to treatment compared to non-users, and knowing whether women used hormonal contraceptives helped the brain wave patterns better predict treatment success. These findings suggest that hormonal contraceptive use, particularly combined oral contraceptives, should be considered when developing personalised depression treatments for women.
© 2026. The Author(s).