Treatment-Resistant Depression in the 21st Century: A Scoping Review of Psychedelics and Neuromodulation in Transforming Care
Premier Journal of Neuroscience May 11, 2026 DOI: 10.70389/pjn.100014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Scoping review Peer reviewed |
|---|---|
| Population | Adults with treatment-resistant depression |
| Interventions | Psilocybin MDMA Ketamine Transcranial magnetic stimulation Electroconvulsive therapy Deep brain stimulation |
| Topics | Anxiety Depression Psilocybin |
| Keywords | Neuromodulation Electroconvulsive therapy Antidepressant Psychological intervention Depression economics Deep brain stimulation Intervention counseling Psychotherapist Clinical psychology Medline Mental illness |
| Key findings | Both psychedelic-assisted therapies and neuromodulation show rapid antidepressant effects in treatment-resistant depression, but evidence for long-term outcomes and comparative effectiveness is limited. |
Abstract
Background: Treatment-resistant depression (TRD) affects a significant proportion of individuals with major depressive disorder and remains difficult to manage with conventional treatments. Psychedelic-assisted therapies and neuromodulation have emerged as innovative interventions targeting neurobiological mechanisms beyond traditional antidepressant approaches.
Objectives: This scoping review mapped current evidence on psychedelic-assisted therapies and neuromodulation for TRD, identified research trends, and highlighted key knowledge gaps.
Methods: Peer-reviewed studies published between 2010 and 2025 were identified from PubMed, PsycINFO, Web of Science, and Scopus. Eligible studies involved adults with TRD receiving psychedelic-assisted therapies (psilocybin, MDMA, ketamine) or neuromodulation interventions (transcranial magnetic stimulation, electroconvulsive therapy, deep brain stimulation). Findings were synthesized narratively with tabular and visual mapping.
Results: Both intervention classes demonstrated rapid antidepressant effects, with psilocybin and ketamine showing fast symptom reduction and neuromodulation, exhibiting consistent efficacy in severe TRD. Evidence for long-term outcomes, comparative effectiveness, and personalized treatment strategies remains limited.