In patients with treatment-resistant depression, a single ketamine infusion shifted belief updating toward a more optimistic bias within 4 hours. This early cognitive change was characterized by stronger asymmetrical reinforcement learning and, after one week of treatment, mediated the clinical antidepressant effect. The findings offer new insights into how fast-acting antidepressants alter cognition, which could be harnessed to promote lasting clinical improvement and treatment responsiveness.
Ketamine infusion makes people with treatment-resistant depression more optimistic about the future by changing how they learn from good and bad news. After a single infusion, patients updated their beliefs more after favorable information and less after unfavorable information, compared to healthy controls. This shift toward optimism was driven by learning more from positive surprises than negative ones. This change in belief-updating predicted early clinical improvement at one week, seen in 19% of patients. The findings suggest ketamine's antidepressant effects involve altering cognitive biases, which could enhance psychotherapy for depression.
Ketamine works quickly as an antidepressant but also causes temporary dissociative symptoms. In everyday clinical settings, it is unclear how much of the antidepressant effect comes from patients' expectations versus from the dissociative experience itself, and how these factors relate to changes in depression over time.