Revisiting Thyroid Function in Patients Undergoing Electroconvulsive Therapy for Severe or Treatment-Resistant...

Background/Objectives: Evidence regarding the relationship between thyroid function tests (TFTs) and severe or treatment-resistant depression in euthyroid individuals remains limited. We aimed to investigate thyroid function tests (TFTs) in euthyroid patients with depression undergoing electroconvulsive therapy (ECT), evaluate associations with ECT response and depression severity, and explore whether clinically meaningful subgroups with differential thyroid function patterns can be identified. Methods: In this retrospective cohort study, we screened 107 inpatients who received ECT for severe or treatment-resistant depression (major depressive disorder [MDD] or bipolar disorder [BD]). Seventy-six euthyroid patients were analyzed. Clinical data, Hamilton Depression Rating Scale (HAMD) scores, and TFTs (TSH, free-T3, and free-T4) were assessed. Logistic regression, multiple linear regression and unsupervised hierarchical cluster analyses were performed. The cluster analysis used clinical and demographic variables, excluding TFTs to avoid circularity and allow thyroid parameters to be examined as secondary biological correlates. Results: The TFT results were not significantly associated with ECT response in euthyroid patients. The multiple linear regression revealed that the baseline HAMD scores were positively associated with free-T4 (β = 0.797, p = 0.001). Hierarchical clustering identified two subgroups; one group characterized by male sex, psychotic features, and MDD diagnosis exhibited lower TSH levels (2.12 vs. 1.49 mlU/L, Cohen's d = 0.56) despite similar ECT response rates. Conclusions: Subtle TFT variations were not associated with ECT response but were related to depression severity and clinical phenotypes. These findings suggest that normal-range thyroid hormone variability may reflect state-related neuroendocrine patterns rather than predictors of treatment outcome. Our results should be regarded as hypothesis-generating and underline the need for prospective studies to clarify the clinical significance of thyroid function variability in severe depression.