SUBGROUP ANALYSIS IN CHANGES IN QUALITY OF LIFE AND DEPRESSION SEVERITY SCORES BY LINE OF THERAPY IN PATIENTS TREATED WITH ESKETAMINE IN A REAL-WORLD SETTING ACROSS ANZ
Authors: Barton *David , Puig Andrea , King Jarrad , Hickie Ian 
Published: February 2025

Abstract

Background
Treatment resistant Major Depressive Disorder (MDD) can be accompanied by lengthy and ineffective treatment periods that prolong patient suffering, reduce expectations of remission and reinforce negative cognitions (Leuchter 2009). Esketamine (a NMDA receptor antagonist) has been approved in Australia and New Zealand (ANZ) as a third-line antidepressant (AD) treatment to provide clinicians with an additional therapeutic option for this population.

Aims and Objectives
This analysis describes the changes among subgroups stratified by previous treatment lines in quality of life, depression severity scores and productivity of patients treated with esketamine in a real-world setting across ANZ.

Method
Participants were recruited from an esketamine Early Access Program. To be eligible, patients must have failed 2 or more oral AD treatments of adequate dose and duration and not received neurostimulation treatment within their current depressive episode. Patients received esketamine for 16 weeks in the study. Outcomes were obtained for Assessment of Quality-of-Life scale (AQoL-8D), Hamilton Depression Rating Scale (HAM-D) and Work and Productivity Activity Index (WPAI). Pre- specified subgroups were classified by number of previous therapies in the same depressive episode (2, 3-5 or 6+).

Results
Of 108 total participants, 22.9% had received 2 prior therapies vs 48.6% and 28.5% who had 3- 5 and 6 or more therapies respectively within their current depressive episode. There were statistically significant differences (p&lt;0.01) for all subgroups in HAM-D scores from baseline to week 16. The subgroup with 2 prior therapies exhibited the largest HAM-D improvement of -11.1 points, (SD 6.6) when compared to the 6+ therapy subgroup which obtained a statistically significant smaller HAM-D improvement of -5.2 points (SD 6.3), p &lt;0.01. The improvement in the 3-5 prior therapies group was in the middle of the other 2 subgroups, -8.0 points (SD 6.7) and not significantly different to either of the two other subgroups. The AQOL improvements from baseline were also robust and statistically significant across all sub-groups with the largest improvement seen in patients who had failed no more than two lines of therapy, albeit no statistical significance could be observed within subgroups.

Discussion and Conclusion
The improvements in AQOL and HAM-D were significant across all sub-groups, with the highest improvement seen in patients who had received only two prior lines of therapy, which might indicate that patients benefit most from an early esketamine treatment. Taken together, the results suggest that patients might benefit more from esketamine earlier in disease treatment, however further studies are warranted.

References
1. Leuchter AF, Cook IA, Hunter AM, Korb AS. A new paradigm for the prediction of antidepressant treatment response. Dialogues Clin Neuroscience. 2009;11(4):435-46.