A six-month observational study of 36 patients with treatment-resistant depression found that those with poor mentalization abilities at the start had more severe depressive symptoms throughout treatment with esketamine. Greater cognitive rigidity appeared protective, possibly by stabilizing emotions and reducing negative thinking. The findings suggest esketamine may help break cognitive inflexibility and improve mentalization, supporting a personalized approach to treatment-resistant depression.
In treatment-resistant depression, esketamine—a glutamatergic modulator approved in 2019—may improve not only depressive symptoms but also key psychological factors such as mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity. In a six-month observational study of 36 patients with treatment-resistant depressive episodes, depressive symptoms significantly decreased, as measured by the Montgomery-Åsberg Depression Rating Scale. By six months, 69% of patients achieved remission, indicating a robust and sustained response. The findings suggest esketamine may be particularly beneficial in reducing cognitive rigidity and improving mentalization, potentially breaking the inflexible thinking patterns that sustain depression. Personalized treatment approaches are emphasized.