Author(s): Cohen, Rebeca ; Bastos, João ; Cunha, Catarina ; Marguilho, Miriam ; Sancho, Ana ; Silva, Maria João Matos ; King, Franklin ; Castro-Rodrigues, Pedro
Date: 2026
Persistent ID: http://hdl.handle.net/10362/200764
Origin: Repositório Institucional da UNL
Subject(s): Antidepressant; Ego dissolution; Ketamine; Psychotherapy; Treatment-resistant depression; Psychiatry and Mental health; SDG 3 - Good Health and Well-being
Ketamine, an N -methyl- d -aspartate antagonist, shows promise for treatment-resistant depression (TRD), with psychedelic doses potentially enhancing efficacy. However, its transient antidepressant effects and the need for repeated infusions raise concerns about optimal duration and long-term safety. Two clinical trials have tested the combination of ketamine with psychotherapy for depression, with mixed results. While real-world data on ketamine infusion protocols exist, reports on clinical outcomes, long-term follow-up, and the role of subjective experiences when ketamine is combined with psychotherapy are limited. This real-world case series examines 12 TRD patients treated with a novel protocol combining ketamine (0.5–1.5 mg/kg IM, total 5–8 sessions) and brief psychodynamic psychotherapy. Response and remission rates were 67% and 58%, respectively, with 50% maintaining remission at 3-month and 1-year follow-ups. Ego dissolution during session 3 correlated with symptom improvement and psychological insight. Our results highlight the therapeutic potential of combining ketamine with psychotherapy to optimize clinical outcomes.
