This observational case-control study (n=60) aims to understand the brain mechanisms involved in belief updating about the future in patients with treatment-resistant depression (TRD) before and after starting ketamine treatment.
The study, sponsored by Assistance Publique – Hôpitaux de Paris, seeks to enrol 60 participants diagnosed with TRD, aged between 18 to 70 years. Participants must have major depressive disorder (MDD) according to DSM5 criteria, with a MADRS score of ≥20 and resistance to at least two different antidepressant treatments. Patients will undergo functional magnetic resonance imaging (fMRI) before or 24 hours after a single subanaesthetic ketamine infusion.
The main outcome measure will be the blood oxygenation level-dependent (BOLD) signal measured with fMRI. Secondary outcome measures include assessing belief updating on the behavioural level, clinical improvement measured by the MADRS scale, and prognostic expectancy rating of antidepressant efficacy.
The study is designed as an observational case-control model with a prospective time perspective. It aims to provide insights into the neurocognitive mechanisms of belief updating in depressed patients and how these mechanisms may contribute to clinical improvement following ketamine antidepressant treatment.
Trial Details
Major depressive disorder (MDD) is characterized by a cognitive triad of negative beliefs about oneself, the future and the world. For example, depressed patients hold persistently negative expectations about the future, despite contradictory evidence, and these strong negative beliefs are thought to play an important role in the maintenance of depressive symptoms and potentially in treatment resistance. Indeed, one out of three patients with major depressive disorder does not respond to conventional, monoaminergic treatments, which has led to the concept of treatment resistant depression (TRD). It is unknown how the brain encodes the strong negative beliefs that are insensitive to positive disconfirming information in TRD patients, and how these neural underpinnings of maladaptive belief updating are altered by antidepressant treatment. The principal objective of this study is to gain insight into the brain mechanisms of belief updating about the future in TRD patients before and after starting ketamine treatment. The results of this study are expected to provide a better understanding of the neurocognitive mechanisms of belief-updating in depressed patients, and how these mechanisms contribute to clinical improvement following ketamine antidepressant treatment.NCT Number NCT05577247