Rapid-acting and neuromodulatory interventions for treatment-resistant OCD: clinical implications in stress reduction

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.