Ketamine Combined With Psychotherapy as a Treatment for Resistant Depression in a Public European Hospital.
Filipa Alves Da Silva, Rita Avelar, Bernardo Peixoto, Leonor Bacelar-Nicolau, Francisco R. Santos, João Costa Ribeiro, Maria João Heitor
Brain and Behavior 2026 DOI: 10.1002/brb3.71164 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pilot proof-of-concept study Peer reviewed |
|---|---|
| Sample size | 9 |
| Population | Patients with treatment-resistant depression at a general hospital within the Portuguese National Health Service |
| Interventions | Ketamine infusion Psychotherapy |
| Duration | 8-week intervention, 3-month follow-up |
| Topics | Ketamine Depression Esketamine |
| Keywords | Off‐label ketamine Psychedelic‐assisted therapy Psychotherapy Resistant depression Response rates Treatment |
| Key points | After eight weeks of ketamine infusions combined with psychotherapy, all nine participants showed reduced PHQ-9 scores, with 44% achieving a treatment response and over half of those with suicidal ideation experiencing remission. |
Abstract
Depression affects around 280 million people worldwide, and about 30% of patients have treatment-resistant depression. Ketamine has significant scientific evidence supporting its use as an antidepressant, making it a promising approach for treatment-resistant cases. Combining ketamine with psychotherapy may enhance therapeutic response and support longer-lasting cognitive and behavioral change. This pilot proof-of-concept study aims to evaluate the effect of treatment with ketamine infusion combined with psychological intervention in a sample of nine patients with treatment-resistant depression at a general hospital within the Portuguese National Health Service. Clinical outcomes were measured through the clinical interview and the patient health questionnaire (PHQ-9) to assess complete or partial improvement. Following eight weeks of treatment, all showed a reduction in their PHQ-9 scores, with the median score transitioning from a baseline categorization of "severe" depression to a "moderate" level. It was found that 44.4% (4/9) of participants showed a response to treatment (≥ 50% reduction in the PHQ-9 score). Among the patients with suicidal ideation, slightly over half showed remission of these thoughts at the end of treatment. Among the participants subsequently monitored as outpatients, only 29% (2/7) experienced a deterioration in mood within three months post-treatment, requiring an adjustment of antidepressant therapy. In our study, an improvement in depressive symptoms was observed, despite their severity, in a sample submitted to multiple previous pharmacological strategies.This retrospective study evaluated ketamine infusions combined with psychotherapy in nine patients with treatment-resistant depression at a general hospital. After eight weeks, all participants improved, with PHQ-9 scores shifting from severe to moderate. Overall, 44% responded to treatment, and among those with suicidal ideation, more than half showed remission.