From rapid response to real-world readiness: Safety monitoring, maintenance strategies, and implementation outcomes for emerging treatments in treatment-resistant depression: A narrative review
Year: 2026
Type: review
Abstract: Background : Treatment-resistant depression (TRD) remains a major therapeutic challenge despite advances in pharmacotherapy and neuromodulation. Rapid-acting treatments, including ketamine and esketamine, have expanded treatment options, while psychedelic-assisted interventions and accelerated repetitive transcranial magnetic stimulation (rTMS) continue to develop. However, rapid symptom improvement does not necessarily translate into sustained remission, functional recovery, or accessible long-term care. Objective : This narrative review examines emerging treatments for TRD, emphasizing safety monitoring, maintenance and discontinuation strategies, patient-centred outcomes, and implementation challenges. Findings : Evidence supports the rapid antidepressant effects of ketamine and esketamine in appropriately selected patients, although treatment durability and maintenance requirements differ. Esketamine has randomized evidence supporting relapse prevention among selected responders, while long-term extension studies provide additional, albeit limited, safety information. Psilocybin-assisted interventions show promising antidepressant effects, but uncertainties remain regarding long-term outcomes, psychological support, and generalizability. Accelerated and connectivity-guided neuromodulation may reduce treatment burden, although further replication and longer follow-up are required. Across treatment approaches, patient selection, adverse-event surveillance, relapse prevention, affordability, and service capacity influence clinical translation. Conclusion : Sustainable progress in TRD requires more than demonstrating acute efficacy. Standardized safety reporting, individualized maintenance planning, longitudinal assessment of functional outcomes, and implementation research are essential to establish whether emerging treatments can deliver safe, durable, and equitable benefits in routine psychiatric practice.
Author: Anil Dhakal
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7226030337