Ketamine Combined With Psychotherapy as a Treatment for Resistant Depression in a Public European Hospital

ABSTRACT Purpose 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. Methods Clinical outcomes were measured through the clinical interview and the patient health questionnaire (PHQ‐9) to assess complete or partial improvement. Results 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. Conclusion 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.