Working Mechanisms and Effectiveness of IV Ketamine-assisted Psychotherapy on Depression in TRD Clients

This open-label observational trial (n=120) will evaluate the effectiveness and underlying mechanisms of intravenous ketamine-assisted psychotherapy in adults aged 18 to 70 years with treatment-resistant depression. The study will assess whether this combined treatment approach can reduce depressive symptoms in people who have not responded adequately to at least two antidepressant treatments and one evidence-based psychotherapy, or who have not improved after at least three consecutive treatment steps under the Dutch multidisciplinary guideline for depression. Participants will undergo a structured programme that includes psychological and psychiatric assessment, medical screening, preparation sessions, ketamine administration sessions, and post-session integration therapy. Ketamine is given intravenously in a supervised clinical setting with monitoring of blood pressure, heart rate, and oxygen saturation, and participants remain under observation until clinically stable. Outcomes include the Beck Depression Inventory measured at baseline, pre-intervention, post-intervention at the end of treatment, and 3 months afterwards.