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 Nóbrega De Almeida, Luiz Felipe Dantas Pereira, David Cavalcante Barbosa, Bruna Santos De Carvalho, Eduardo Igor Torquato Cardoso Lopes, Ariadne Cruz De Oliveira, Draulio Barros de Araujo, Fernanda Palhano-Fontes, Gisele Fernandes-Osterhold, Nicole Galvão-Coelho
medRxiv Preprint Server May 31, 2026 preprint DOI: 10.64898/2026.05.31.26354555 via medRxiv
Summary
Ketamine is an effective rapid-acting treatment for treatment-resistant depression (TRD), showing significant antidepressant effects within hours. Its ability to enhance neuroplasticity and psychological openness suggests that combining it with psychotherapy could improve emotional processing and cognitive restructuring. However, the potential benefits of adding structured psychotherapeutic support to ketamine treatments have not been thoroughly investigated.
Study at a glance
| Key finding | The adjunctive potential of structured psychotherapeutic support in ketamine-based interventions remains largely unexplored. |
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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.