COMPARABLE SYMPTOM IMPROVEMENT WITH ELECTROCONVULSIVE THERAPY AND ESKETAMINE IN TRANSGENDER AND GENDER NON-CONFORMING ADULTS WITH TREATMENT-RESISTANT DEPRESSION

Background

Transgender and gender non-conforming adults have higher prevalence and severity of depressive disorders than cisgender adults, with increased rates of anxiety, PTSD, substance use, and suicidality. Emerging data suggest greater severity and suicidality among those seeking care for treatment-resistant depression (TRD). Electroconvulsive therapy (ECT) and esketamine are effective for TRD: ECT remains the gold standard with 60–80% response and 50–60% remission rates, while esketamine provides rapid antidepressant effects and is FDA-approved for TRD and depressive symptoms with acute suicidal ideation/behavior. No prior studies have examined or compared outcomes in gender non-conforming or transgender adults.

Methods

Adults with TRD who self-identified as gender non-conforming or transgender were included in a retrospective chart review using data from a large academic center. Two cohorts were analyzed: (1) 9 patients receiving esketamine (5 gender non-conforming, 3 transgender male, 1 transgender female); (2) 9 receiving ECT (4 gender non-conforming, 3 transgender male, 2 transgender female). Montgomery–Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology (QIDS) scores were measured at baseline and after 8 sessions. Paired-sample t-tests assessed changes.

Results

In the esketamine group, MADRS improved from 37.44 (SD=10.31) to 25.00 (SD=14.92), t(8)=–3.29, p=.005. QIDS improved from 21.00 (SD=3.39) to 12.78 (SD=7.74), t(8)=–3.74, p=.002. In the ECT group, MADRS improved from 37.89 (SD=7.81) to 25.56 (SD=13.32), t(8)=–3.39, p=.005. QIDS improved from 20.67 (SD=4.21) to 13.56 (SD=7.49), t(8)=–3.03, p=.008.

Conclusion

In this preliminary analysis of transgender and gender non-conforming adults with TRD, both esketamine and ECT were associated with significant comparable reductions in depressive symptom severity after eight treatments. Rather than indicating a single preferred modality, these findings suggest that multiple evidence-based treatment pathways may yield meaningful clinical improvement for gender diverse patients. Extending beyond traditional efficacy framing, the results support flexible, individualized TRD treatment approaches in populations historically underrepresented in clinical research. Larger prospective studies are needed to confirm these observations and further characterize treatment response across gender identities.