ketamine has gained attention for its rapid
antidepressant effects, researchers are increasingly exploring whether pairing it with psychotherapy can enhance and sustain clinical benefits. In this context, Filipa Alves da Silva and colleagues from the Department of Psychiatry and Mental Health at Hospital Beatriz Ângelo in Loures, Portugal, evaluated ketamine-assisted psychotherapy within the Portuguese National Health Service.
The retrospective proof-of-concept study included nine adults with treatment-resistant depression who had failed several pharmacological therapies. Patients received ketamine infusions alongside psychological intervention over eight weeks. Clinical outcomes were assessed through interviews and the Patient Health Questionnaire-9 (PHQ-9), a validated measure of depressive symptom severity.
• All participants demonstrated clinical improvement by the end of the treatment period.
• Median PHQ-9 scores shifted from the severe depression category at baseline to moderate levels after eight weeks.
• Nearly 44% of patients achieved a treatment response, defined as a reduction of at least 50% in PHQ-9 scores.
• Among patients with suicidal ideation at baseline, more than half experienced remission of these thoughts by the end of the intervention.
• Follow-up findings indicated sustained benefits beyond treatment, with only two of seven monitored patients experiencing mood deterioration within three months, necessitating adjustments to antidepressant therapy.
The authors emphasized that these improvements were observed despite the severity and chronic nature of depression in the study population. However, they also highlighted important limitations. The small sample size limits generalizability, and the absence of a control group makes it difficult to separate the effects of ketamine from those of psychotherapy alone. Additional constraints included reliance on a single self-report scale, lack of standardized diagnostic interviews, and no formal assessment of psychotherapy fidelity.
Despite these limitations, the study offers early real-world evidence supporting the feasibility of ketamine-assisted psychotherapy in a public hospital setting. The findings highlight the need for larger, controlled trials to confirm efficacy, identify key therapeutic mechanisms, and define the long-term role of this combined approach in managing treatment-resistant depression.
Avelar, R., Peixoto, B., Bacelar-Nicolau, L., Santos, F., Ribeiro, J. C., & Heitor, M. J. (2025). Ketamine Combined With Psychotherapy as a Treatment for Resistant Depression in a Public European Hospital. Brain and Behavior, 16(1), e71164. https://doi.org/10.1002/brb3.71164
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