1. Ketamine use in patients with treatment-resistant depression resulted in more belief-updating that was optimistically biased.

Evidence Rating Level: 3 (Average)

Major depressive disorder (MDD) continues to be a significant public health concern and is often characterized by maladaptive negative beliefs about oneself and the future. A significant portion of patients with depression do not improve with traditional antidepressant medications, a phenomenon referred to as treatment-resistant depression (TRD). In recent years, ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, has been thought to be a treatment option for TRD. However, the effect of ketamine on improving cognitive beliefs is not known. In this observational case-control study, patients with TRD and healthy volunteers were administered ketamine in a clinical care setting. The primary outcome assessed was belief updating which was measured by a specialized belief-updating task. The results of this study showed that after the first ketamine infusion, patients with TRD changed their beliefs more positively than the control group (β = −0.91, 95%CI −1.58 to −0.24). This resultant optimism bias in beliefs was correlated with fewer depressive symptoms that were measured by the Montgomery-Asberg Depression Rating Scale (MADRS) score following one week of treatment. In conclusion, these findings suggest that ketamine may improve cognitive beliefs in patients with treatment-resistant depression. However, several limitations exist in the methodology of this study. Firstly, it is difficult to discern whether ketamine similarly improved optimism bias in the healthy controls as well as the patients with TRD. As well, as participants in this study used ketamine in addition to their pre-existing antidepressant therapies, the drug interactions with ketamine are unknown. Nevertheless, these findings articulating the belief-updating processes of ketamine in treatment-resistant depression are interesting and could have important implications for augmenting psychotherapy.

Click to read the study in JAMA Psychiatry

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