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.