Personalizing esketamine treatment in TRD and TRBD: the role of mentalization, cognitive rigidity, psychache, and suicidality.
Miriam Olivola, Filippo Mazzoni, Barbara Tarantino, Alessandro Guffanti, Matteo Marcatili, Monica Macellaro, Nicolaja Girone, Vassilis Martiadis, Fabiola Raffone, Tiziano Prodi, Natascia Brondino, Giovanni Martinotti, Massimo Clerici, Roberta Anniverno, Bernardo Dell'osso
Frontiers in psychiatry January 1, 2025 Peer reviewed DOI: 10.3389/fpsyt.2025.1736114 via PubMed
Summary
Esketamine treatment for patients with treatment-resistant depression (TRD) led to significant improvements in depressive symptoms and various psychological factors over six months. Notably, 69% of the patients achieved remission, and enhancements were observed in mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity. These results suggest that esketamine may help reduce cognitive rigidity and improve emotional processing, emphasizing the need for personalized treatment strategies.
Study at a glance
| Design | prospective multicenter observational study |
|---|---|
| Sample size | 36 |
| Population | patients with treatment-resistant depressive episodes, including TRD and TRB |
| Key finding | A significant improvement in depressive symptoms was observed, with 69% of patients achieving remission by six months. |
Abstract
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, was 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 and social cognition, and promoting resilience. This prospective multicenter observational study aimed to evaluate esketamine's therapeutic impact on both depressive symptoms and key psychological factors-including mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity-that could predict treatment response and enable a more personalized approach to TRD and TRBD management. Thirty-six treatment-resistant depressive episode patients, including TRD and TRB, 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. A significant improvement in depressive symptoms was observed, as indicated by a reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) scores over time. Moreover, improvement was observed in different key psychological domains, such as mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity. By six months, 69% of patients achieved remission, confirming a robust and sustained therapeutic response. These findings highlight the importance of a personalized treatment approach in treatment- resistant depressive episode patients. 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 treatment-resistant depressive episode patients.