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

Rebeca Cohen, João Bastos, Catarina Cunha, Miriam Marguilho, Ana Sancho, Maria João Matos Silva, Franklin King, Pedro Castro-Rodrigues

General Hospital Psychiatry 2026 DOI: 10.1016/j.genhosppsych.2026.02.001 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Case series Case report Peer reviewed
Sample size 12
Population Patients with treatment-resistant depression
Interventions Ketamine Brief psychodynamic psychotherapy
Dose 0.5-1.5 mg/kg IM
Duration 5-8 sessions; 3-month and 1-year follow-ups
Topics Depression Ego dissolution Ketamine Esketamine
Keywords Antidepressant Psychotherapy
Citations 1
Key findings Combining ketamine with brief psychodynamic psychotherapy yielded 67% response and 58% remission rates, with half of patients maintaining remission at one year, and ego dissolution during session 3 correlated with improvement.

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.

In the evidence

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  • Combining ketamine with brief psychodynamic psychotherapy yielded 67% response and 58% remission rates, with half of patients maintaining remission at one year, and ego dissolution during session 3 correlated with improvement.

    Synthesized

Comparable studies

Other case reports and case series on ketamine for depression, most cited first.

Study Year Design Participants
Electroconvulsive Therapy, Ketamine, and Esketamine in a Patient with Major Depressive Disorder and Multiple Comorbidities: A Case Report over 10-year Treatment from Adolescence to Adulthood. A patient with treatment-resistant depression and comorbid generalized anxiety... 2025 Case report n = 1
A longitudinal case series of IM ketamine for patients with severe and enduring eating disorders and comorbid treatment‐resistant depression Patients with enduring eating disorders and treatment-resistant depression 2021 Case series n = 4
Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series Veterans with co-morbid depression and PTSD 2022 Retrospective case series n = 35
Case report: Intramuscular ketamine or intranasal esketamine as a treatment in four patients with major depressive disorder and comorbid anorexia nervosa Patients with anorexia nervosa and a comorbid depressive disorder treated at a private... 2023 Case report n = 4
Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder Patients with treatment-resistant depression and comorbid PTSD 2023 Case series n = 5

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