Rapid-acting and neuromodulatory interventions for treatment-resistant OCD: clinical implications in stress reduction
Johan Saelens, Franziska Stadler, Victoria Forschauer, Juan Carlos Baldermann, Ioline D. Henter, Carlos A. Zarate, Christoph Kraus
Translational Psychiatry September 28, 2026 DOI: 10.1038/s41398-026-04480-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Peer reviewed |
|---|---|
| Interventions | Ketamine Psilocybin Repetitive transcranial magnetic stimulation (rTMS) Deep brain stimulation (DBS) |
| Key findings | The review reports that preliminary trials of rapid-acting agents such as ketamine and psilocybin in OCD are encouraging, but results are mixed and evidence for repeated dosing is scarce. It also highlights growing evidence linking early life stress to neuroinflammatory pathways and HPA-axis dysregulation in OCD, which the authors propose as novel treatment targets alongside neuromodulatory approaches like rTMS and DBS. |
Abstract
Obsessive-compulsive disorder (OCD) is a highly debilitating and often chronic condition. A large percentage of patients do not respond to first-line treatments with selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy (CBT), underscoring the need for novel therapeutic approaches. In this context, promising innovative treatments have recently emerged for OCD; these include pharmacological options such as ketamine and psilocybin—which may exert rapid-acting effects—as well as neuromodulatory treatments such as repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS). In addition, growing evidence links early life stress with neuroinflammatory pathways and dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in OCD, opening novel treatment targets. While preliminary clinical trials of novel rapid-acting substances in OCD are encouraging, results are mixed and evidence of repeated dosing is scarce. This narrative review synthesizes current evidence on rapid-acting and neuromodulatory treatments for OCD, with a particular focus on stress-related mechanisms, offering new therapeutic possibilities as well as avenues for future research.