Comparing transcranial magnetic stimulation and esketamine treatment response trajectories in resistant depression.
Lindsay L Benster, Jordan N Kohn, Benjamin Wade, Noah Stapper, Cory R. Weissman, Jean-Philippe Miron, Zafiris J Daskalakis, Lawrence G Appelbaum
Journal of Affective Disorders June 7, 2026 DOI: 10.1016/j.jad.2026.122107 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective analysis Peer reviewed |
|---|---|
| Sample size | 372 |
| Population | Adults with treatment-resistant depression treated at UC San Diego Health |
| Interventions | Repetitive transcranial magnetic stimulation Intranasal esketamine |
| Duration | 90-day follow-up |
| Topics | Depression Esketamine |
| Keywords | Rtms |
| Key points | Intranasal esketamine was associated with faster antidepressant and anti-suicidal response than rTMS, but overall efficacy at 90 days was similar. |
Abstract
Repetitive 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. A 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). Esketamine 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. Esketamine 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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: Esketamine Supports
Intranasal esketamine was associated with faster antidepressant and anti-suicidal response than rTMS, but overall efficacy at 90 days was similar.
Synthesized
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.