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 January 1, 2026 DOI: 10.1016/j.genhosppsych.2026.02.001 via PubMed
Summary
AI-generated from the abstractA case series of 12 patients with treatment-resistant depression treated with a novel protocol combining ketamine injections (0.5-1.5 mg/kg intramuscularly, 5-8 sessions) and brief psychodynamic psychotherapy found that 67% responded and 58% achieved remission. Half of the patients maintained remission at 3-month and 1-year follow-ups. Ego dissolution during the third ketamine session correlated with symptom improvement and psychological insight. The results suggest that combining ketamine with psychotherapy may enhance and prolong antidepressant effects beyond ketamine alone.
Study at a glance
| Characteristics | Case series Case report Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Patients with treatment-resistant depression |
| Topics | Depression Ego dissolution Ketamine |
| Keywords | Antidepressant Psychotherapy |
| Citations | 1 |
| Key finding | 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.