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.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cites 8
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
- Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent The Journal of Clinical Psychiatry May 11, 2020
and 3 more in the library