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Can we change depressive beliefs? Modulation of belief updating by ketamine in treatment resistant depression

Hugo Bottemanne, Orphée Morlaàs, Anne Claret, Philippe Fossati, Liane Schmidt

preprint DOI: 10.31234/osf.io/zx5vr (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort
Sample size 56
Population Treatment-resistant depression patients and healthy controls
Intervention sub-anesthetic ketamine infusion
Duration Single infusion, one-week follow-up
Topics Depression Esketamine Ketamine
Citations 4
Key findings A single ketamine infusion shifted belief-updating toward optimism in treatment-resistant depression patients, and this change mediated early clinical response.

Abstract

Treatment resistant depression (TRD) is a tremendous health problem that has encouraged novel treatment strategies involving sub-anesthetic ketamine infusions. While ketamine induces rapid and sustained clinical improvement, its cognitive effects are less well known. Here we tested if ketamine alters the negative expectancies about the future that are insensitive to disconfirming information, and play a key role for the maintenance of depression. Twenty-six TRD patients performed a belief-updating task before and after ketamine treatment, and were compared to a group of thirty healthy controls. The task involved estimating likelihoods of experiencing adverse life events before and after receiving information about the actual occurrence of events in the general public. A computational reinforcement-learning (RL) model tested how much belief updating was explained by learning from positive (better than thought) and negative (worser than thought) estimation errors. Global clinical improvement was assessed by the Montgomery Asberg Depression scale (MADRS). Following a single ketamine infusion patients updated their beliefs about the future more after favorable, and less after unfavorable information, controlled for sequential testing effects by comparison to healthy controls. The emergence of optimism biases in belief updating was underpinned by asymmetric learning from positive rather than negative estimation errors, and formally mediated precocious clinical responsiveness at one week of treatment observed in 19% of the patients. These findings provide novel insight into the cognitive mechanisms of ketamine action in TRD, and through it open the window toward promising perspectives for augmented psychotherapy in mood disorder.

Comparable studies

Other observational and cohort studies on ketamine for depression, most cited first.

Study Year Design Participants
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30
Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... 2017 Observational cohort n = 59
Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... 2014 Post hoc analysis of pooled data from four studies n = 108
An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder 2011 Observational cohort n = 14
Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... 2019 Observational cohort n = 25

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