Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study

Sep 4, 2025Journal of affective disorders

How Thinking About Feelings and Mental Flexibility May Predict Esketamine's Effects in Hard-to-Treat Depression

AI simplified

Psychedelic Science on OpenScience ↗PubMed ↗DOI ↗

Abstract

Thirty-six patients with treatment-resistant depression were assessed over six months after receiving esketamine.

A link was found between mentalization deficits and more severe depressive symptoms.
Patients with lower mentalization skills had higher scores on the depression scale both initially and during follow-up.
Greater cognitive rigidity may help reduce negative thinking and support emotional stability.
Esketamine might improve mentalization and decrease cognitive inflexibility, which could help with persistent depressive thoughts.
Personalized treatment approaches for treatment-resistant depression may be enhanced by understanding these psychological factors.

AI simplified

INTRODUCTION: Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes, improving mentalization, social cognition and promoting resilience.

OBJECTIVE: This prospective multicenter observational study aimed to evaluate esketamine's therapeutic impact on depressive symptoms and explore whether psychological and clinical factors-including mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity-could predict treatment response, enabling a more personalized approach to TRD management.

METHODS: Thirty-six TRD patients treated with esketamine were assessed over a six-month follow-up period using psychometric measures of depression severity, suicidality, mentalization, social cognition, psychache, and cognitive-emotional rigidity.

RESULTS: A significant association emerged between mentalization deficits and depressive symptoms. Specifically, patients with poor baseline mentalization abilities exhibited higher Montgomery-Åsberg Depression Rating Scale (MADRS) scores both at baseline and throughout follow-up. In contrast, greater cognitive rigidity appeared to have a protective role, potentially mitigating negative thinking and providing emotional stability, which may enhance resilience to stressors.

CONCLUSIONS: These findings highlight the importance of a personalized treatment approach in TRD. Esketamine may be particularly beneficial in reducing cognitive rigidity, improving mentalization, and breaking the cognitive inflexibility that contributes to sustained negative depressive thinking patterns. Further research is needed to refine patient stratification and optimize treatment strategies for individuals with TRD.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the psychedelic science brief