ArticleJournal of affective disorders2026
Comparing transcranial magnetic stimulation and esketamine treatment response trajectories in resistant depression.
Article in Journal of affective disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveRepetitive transcranial magnetic stimulation (rTMS) and intranasal esketamine are FDA-approved for treatment-resistant depression (TRD), yet comparative real-world data on response trajectories and predictors of outcomes remain limited.
methodsA retrospective analysis was performed using electronic medical records from UC San Diego Health. Adults with TRD treated with rTMS (n = 279) or intranasal esketamine (n = 93) between 2017 and 2025 were included. The primary outcome was clinical response (≥50% PHQ-9 reduction). Time-to-response was assessed using inverse probability treatment weighted (IPTW) Cox models; Kaplan-Meier curves and log-rank tests provided descriptive comparisons. Covariates included age, trauma history, anxiety comorbidity, benzodiazepine use, tobacco use history, BMI, and baseline symptom severity. Secondary outcomes included remission (PHQ-9 < 5) and suicidal ideation (SI).
resultsEsketamine demonstrated earlier response over 90 days (RMST difference = -11.94 days) and faster time-to-response in the IPTW Cox model (HR = 1.62, p = 0.005); KM estimates showed median response at 36 vs. 49 days (p = 0.0096) with convergence by ∼90 days. Cumulative response and remission rates were numerically higher for esketamine (68.8% / 45.2%) than rTMS (59.4% / 40.1%), supporting a speed-of-response difference rather than superior overall efficacy. SI improved more rapidly with esketamine (median 9 vs. 26 days; p = 0.001). In the rTMS cohort, comorbid anxiety (HR = 0.69, p = 0.039) and benzodiazepine use (HR = 0.73, p = 0.046) predicted slower response, while former tobacco use predicted faster response (HR = 1.31, p = 0.006). No significant predictors emerged for esketamine.
conclusionsEsketamine was associated with earlier observed antidepressant and anti-suicidal improvement than rTMS. Baseline factors, including benzodiazepine use, may help inform expectations regarding rTMS response trajectory.
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