Preliminary Non-Randomized Clinical Trial of Subcutaneous Esketamine in Treatment-Resistant Depression: Exploring Adjunctive Effects of Ketamine-Assisted Psychotherapy
Yves Martins Varela, Patrícia Cavalcanti-Ribeiro, Geovan Menezes de Sousa, Marcelo Falchi-Carvalho, Juliana Dos Santos Fernandes Barbalho, Raynara Bolcont De Oliveira Gomes, Melanie Moura Medina Gurgel, Bruno Carvalho Pereira, Pâmela Milena De Lima Souza, Kaike Thiê da Costa Gonçalves, Mariana Muniz, Victor Rocha Nobrega de Almeida, Luiz Felipe Dantas Pereira, David Cavalcante Barbosa, Bruna Santos De Carvalho, Eduardo Igor Torquato Cardoso Lopes, Ariadne Cruz De Oliveira, Dráulio Barros de Araújo, Fernanda Palhano-Fontes, Gisele Fernandes-Osterhold, Nicole Galvão-Coelho
medRxiv Preprint Server May 31, 2026 preprint DOI: 10.64898/2026.05.31.26354555 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review |
|---|---|
| Population | Treatment-resistant depression patients |
| Topics | Depression Esketamine Ketamine Psychedelic-assisted therapy |
| Key findings | Ketamine's capacity to induce neuroplasticity and psychological openness suggests psychotherapy could complement its pharmacological effects, but the adjunctive potential remains largely unexplored. |
Abstract
Background Ketamine has emerged as an effective rapid-acting treatment for treatment-resistant depression (TRD), producing significant antidepressant effects within hours of administration. Given ketamine’s capacity to induce states of heightened neuroplasticity and psychological openness, psychotherapy may represent a meaningful complement to its pharmacological effects — facilitating emotional processing, cognitive restructuring, and the consolidation of therapeutic gains. However, the adjunctive potential of structured psychotherapeutic support in ketamine-based interventions remains largely unexplored.