Comparative Efficacy and Functional Outcomes of Psychedelic-Assisted Therapies in Treatment-Resistant Depression: A Systematic Review of Recent Clinical Trials.
Cureus April 1, 2025 Ciara Mimms, Kassandra Sotelo, Abdul Saboor Khaliq 1 citation
A systematic review of ten recent randomized controlled trials found that psychedelic-assisted therapies, including ketamine, esketamine, and psilocybin, significantly reduce depressive symptoms in treatment-resistant depression. Oral and intranasal esketamine and high-dose psilocybin showed sustained antidepressant effects. Some trials also reported functional improvements, such as better workplace productivity and cognitive stability, particularly with esketamine. The therapies were well tolerated with minimal cognitive side effects. Risk of bias was low in four studies and moderate in six due to open-label or observational extensions. The findings support psychedelic-assisted therapies as viable alternatives or adjuncts for treatment-resistant depression and emphasize the need to assess both clinical and functional outcomes.