Major Depressive Disorder (MDD) profoundly affects emotional well-being and daily functioning. Initial MDD treatment typically combines antidepressants and psychotherapy. When two treatments fail, more intensive options, like ECT or TMS, are considered. However, there's limited research comparing their efficacy and outcomes.

A retrospective cohort study was performed using deidentified patient data from the TriNetX database. The study focused on individuals diagnosed with MDD who received ECT or TMS at any time post-diagnosis. To ensure comparability, patients were matched for age, sex, race, ethnicity, mental and behavioral disorders, mood and affective disorders, anxiety disorders, substance use disorders, BMI, and concurrent usage of central nervous system medications. Short-term outcomes included disorientation, retrograde amnesia, and headache within one month. Long-term outcomes included the incidence of depressive episodes, suicidal ideations, and suicide attempts between one month and five years post-treatment.

After propensity score matching, both cohorts included 2,916 patients each. Short-term analysis revealed significantly higher rates of disorientation (2.81% vs. 0.41%), retrograde amnesia (0.65% vs. 0.34%), and headache (7.20% vs. 4.36%) in the ECT group (p < 0.01 for all comparisons). In the long-term, patients who underwent ECT exhibited a significantly higher incidence of depressive episodes (53.77% vs. 44.99%), suicide attempts (6.86% vs. 3.98%), and suicidal ideations (23.49% vs. 12.38%) compared to patients treated with TMS (p < 0.01 for all comparisons).

The study suggests that TMS may offer greater long-term efficacy with a more favorable short-term side effect profile compared to ECT for MDD patients. Further research is needed to understand the mechanisms behind these disparities and to optimize the selection of treatment modalities for patients with MDD.