Fast-acting approaches for treatment-resistant depression: real-world comparative effectiveness of Intranasal Esketamine versus accelerated rTMS.
Michele Prato, Matteo Carminati, Filippo Frizzi, Greta Verri, Mattia Tondello, Barbara Barbini, Cristina Colombo, Zanardi Raffaella
Int J Psychiatry Clin Pract March 11, 2026 DOI: 10.1080/13651501.2026.2642680 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective observational study Longitudinal Peer reviewed |
|---|---|
| Sample size | 40 |
| Population | Patients with treatment-resistant depression |
| Interventions | Accelerated repetitive Transcranial Magnetic Stimulation (aTMS) Intranasal Esketamine |
| Duration | Assessments at baseline and 1, 3, and 6 months |
| Measures | Montgomery-Asberg Depression Rating Scale (MADRS) |
| Topics | Depression Esketamine |
| Citations | 1 |
| Key findings | aTMS showed a stronger early antidepressant effect than intranasal esketamine at one month (response 72.2% vs 20%; remission 66.6% vs 10%), but this advantage diminished and was not significant at six months. Psychiatric comorbidities were associated with greater improvement at three and six months within the esketamine subgroup only. |
Abstract
Background: Treatment-Resistant Depression (TRD) often persists despite adequate pharmacotherapy. Intranasal Esketamine and accelerated repetitive Transcranial Magnetic Stimulation (aTMS) are rapid-acting options, but head-to-head comparisons remain limited.
Methods: We conducted a retrospective study on TRD patients receiving either aTMS (n = 18) or Intranasal Esketamine (n = 22). Depression severity (Montgomery-Asberg Depression Rating Scale, MADRS) was assessed at baseline and 1, 3, and 6 months. Primary outcomes were response (≥50% MADRS reduction) and remission (MADRS <10). Longitudinal change was modelled with linear mixed-effects; moderators included clinical and demographics features.
Results: At 1 month, aTMS showed higher response (72.2% vs 20%; p < 0.001) and remission (66.6% vs 10%; p = 0.0031) than Esketamine. Between-group differences were not significant at 3 months or 6 months. Mixed-effects models showed greater MADRS reduction with aTMS at 1 (p < 0.001) and 3 months (p = 0.007), but not at 6 months (p = 0.057). Psychiatric comorbidities were associated with greater improvement at 3 and 6 months within the Esketamine subgroup, with no analogous association in the aTMS subgroup.
Conclusions: aTMS showed a stronger early antidepressant effect, but its advantage over esketamine progressively diminished and was no longer evident at six months. Prospective, well-powered comparative trials are required to validate these findings.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.