Clinical research has demonstrated that persistent negative beliefs preserve depression and that subanesthetic ketamine infusions induce rapid antidepressant effects. A study was recently conducted to examine whether ketamine alters belief updating and how such cognitive effects are associated with the clinical effects of ketamine. The study was an observational case-control protocol with a mixed-effects design that nested 2 groups by 2 testing time points, and the observers were not blinded. The study included patients with treatment-resistant depression (TRD) (unipolar and bipolar) between the ages of 34 to 68 years and age-matched controls. Patients were observed 24 hours before a single ketamine infusion, 4 hours after the infusion, and 4 hours after the third infusion, which was one week after the first infusion. Healthy controls were observed twice, one week apart without ketamine exposure. Of the 56 included participants, a total of 26 patients had TRD. The main outcome was a change in Montgomery-Asberg Depression Rating Scale (MADRS) score and belief updating after patients received good news and bad news measured by a cognitive belief-updating task that was mathematically formalized by a computational reinforcement learning model. A significant group?×?testing time point?×?news valence interaction showed that patients with TRD updated their beliefs more after good than bad news following a single ketamine infusion (controlled for age and education: ß?=?-0.91; 95% CI, -1.58 to -0.24; t216?=?-2.67; P?=?.008) than controls. Additional analysis revealed that this effect was associated with asymmetrical learning rates after ketamine treatment. The learning rates were higher when the participants received good news versus bad news and this was partially mediated by antidepressant responses. The results suggest that ketamine may have implications for cognitive mediation in patients with TRD. Future research is needed.

Reference:

Bottemanne H et al. JAMA Psychiatry 2022; E1-E9. Abstract.