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

Inclusion Criteria: * Adults (18 years and older) * TRD * A MADRS score above the established clinical cut-off, indicating clinically significant depressive symptoms * Insufficient response to at least two adequate antidepressant treatment trials and one evidence-based psychotherapy, or failure to achieve adequate improvement following at least three consecutive treatment steps in accordance with the Dutch Multidisciplinary Guideline for Depression Exclusion Criteria: * Current substance use disorder or recent illicit drug use * Substance use disorder not in remission for at least 3 months * Inability to abstain from alcohol for 24 hours before and after treatment * Acute suicidality * Current or past psychotic disorder * Significant neurological disorders (e.g., epilepsy, elevated intracranial pressure) * Uncontrolled hypertension or medical conditions associated with increased cardiovascular or cerebrovascular risk (e.g., aneurysms, recent myocardial infarction or intracerebral hemorrhage) * Significant bladder disease (e.g., cystitis) * Severe hepatic impairment * Pregnancy, breastfeeding, or ongoing IVF treatment * Extreme underweight or obesity where treatment is deemed medically unsafe Inability to arrange an accompanying adult for transport and support after treatment