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Peer-reviewed article

Ketamine combined with psychotherapy for treatment-resistant depression: Real-world outcomes and the role of subjective experience.

Cohen RiD, Bastos JiD, Cunha C, Marguilho M, Sancho A, Silva MJM, King F 4th, Castro-Rodrigues P

General hospital psychiatryFeb 10, 2026Portugal, United States, United Kingdom1 citationsDOI: 10.1016/j.genhosppsych.2026.02.001

Abstract

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.

Topics & conditions

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KetamineDepression

Keywords

AntidepressantTreatment-resistant DepressionpsychotherapyEgo Dissolution

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