Comparative Efficacy and Functional Outcomes of Psychedelic-Assisted Therapies in Treatment-Resistant Depression: A Systematic Review of Recent Clinical Trials.
Ciara Mimms, Kassandra Sotelo, Abdul Saboor Khaliq
Cureus April 1, 2025 DOI: 10.7759/cureus.82532 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Open-label Peer reviewed |
|---|---|
| Interventions | ketamine esketamine psilocybin |
| Topics | Depression Ketamine Psilocybin Psychedelic-assisted therapy |
| Keywords | Antidepressant response Cognitive effects Depression scales Randomized controlled trial Systematic review Psychedelic medicine Psychedelic treatment Treatment-resistant depression trd Refractory depression Drug-resistant depression Medical studies |
| Citations | 1 |
| Key findings | Psychedelic-assisted therapies, particularly esketamine and high-dose psilocybin, significantly reduce depressive symptoms and improve functional outcomes in treatment-resistant depression. |
Abstract
This systematic review explores the comparative efficacy and functional outcomes of psychedelic-assisted therapies in the management of treatment-resistant depression (TRD). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search was conducted across PubMed, Scopus, and Web of Science for randomized controlled trials (RCTs) published in the last 12 months. Ten RCTs were included, evaluating agents such as ketamine, esketamine, and psilocybin. Most studies demonstrated significant reductions in depressive symptom severity, with oral and intranasal esketamine and high-dose psilocybin showing sustained antidepressant effects. Functional improvements, such as workplace productivity and cognitive stability, were reported in select trials, notably those involving esketamine. Risk of bias was low in four studies and moderate in six due to open-label or observational extensions. Overall, psychedelic therapies were well tolerated, with favorable safety profiles and minimal cognitive adverse effects. These findings support the integration of psychedelic-assisted therapies as viable alternatives or adjuncts in the treatment of TRD and highlight the importance of assessing both clinical and functional endpoints for a more holistic understanding of therapeutic benefit.
Comparable studies
Other systematic reviews and meta-analyses on ketamine and psychedelic-assisted therapy, most cited first.