Early effects predict trajectories of response to esketamine in treatment-resistant depression

This longitudinal study (n=50, confirmatory sample n=55) investigated the use of esketamine in patients with treatment-resistant depression (TRD) and aimed to define distinct response trajectories. The study identified two classes, one representing response and the other non-response, influenced by factors like concomitant benzodiazepine medication, number of depressive episodes, or polarity. After two esketamine administrations, the depression score (MADRS) predicted the 90-day response trajectory with 80% accuracy, suggesting clinicians could use MADRS scores to decide whether to continue treatment in TRD patients.

Abstract of Early effects predict trajectories of response to esketamine in treatment-resistant depression

“Background: The efficacy of esketamine in treatment-resistant depression (TRD) has been confirmed. However, its administration is expensive and restrictive, with limited knowledge on how long the treatment should be continued. Predicting the treatment outcome would benefit patients and alleviate the global treatment cost. We aimed to define distinct trajectories of treatment response and assess their predictability.

Methods: In this longitudinal study, two independent samples of patients with unipolar or bipolar TRD were treated with esketamine in real-world settings. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) before each esketamine administration. Latent class analyses were used to define trajectories of response.

Results: In the original sample (N = 50), we identified two classes whose trajectories depicted response and non-response, respectively. The model was validated in the confirmatory sample (N = 55). Class membership was influenced by a few baseline characteristics such as concomitant benzodiazepine medication, number of depressive episodes or polarity. On the other hand, after only two esketamine administrations, the MADRS score predicted the 90-day trajectory of response with an accuracy of 80 %.

Limitations: This observational study is not placebo-controlled. Therefore, its results and their generalizability need to be confirmed in experimental settings.

Conclusions: After the first administrations of esketamine, the MADRS score has a good capacity to predict the most plausible trajectory of response. While thresholds and their predictive values need to be confirmed, this finding suggests that clinicians could base on MADRS scores their decision to discontinue treatment because of poor remaining chances of treatment response.”

Authors: Isaure Estrade, Anne-Cécile Petit, Vincent Sylvestre, Michel Danon, Sylvain Leroy, Rebecca Perrain, Fabien Vinckier, Lila Mekaoui, Raphaël Gaillard, Emmanuelle Advenier-Iakovlev, Rossella Letizia Mancusi, Daphnée Poupon, Pierre De Maricourt & Philip Gorwood

Summary of Early effects predict trajectories of response to esketamine in treatment-resistant depression