Heterogeneous trajectory of depressive symptoms after repeated subcutaneous esketamine injections

ABSTRACT Background Ketamine is an effective antidepressant with a 65–70% response rate and a fast onset of action. Esketamine (S-ketamine) has been found to be twice as potent as R-ketamine, while inducing fewer adverse effects, such as sedation and cognitive impairment, than racemic ketamine. However, little is known about its heterogeneous effects in treating depression. The aim of this study was to evaluate heterogeneity in the trajectory of depression treated with subcutaneous esketamine. Methods Seventy severely depressed patients were administered repeated subcutaneous esketamine injections, and four assessments on depressive symptoms were performed. A growth mixture model analysis of the sample was utilized to identify potential latent classes. Results Our model revealed two distinct subgroups: responders (79.1%), those who showed a lower depression score at the first time point and a strong decline in symptoms; and non-responders (20.9%), those who showed a higher initial depression score and a limited decline in symptoms. Limitations This study has an observational design, with possible confounders. We were unable to analyse class differences in baseline symptoms, probably due to sample size. The group behaviour observed here must be confirmed with different populations. There is currently no clear cutoff to predict group membership. Conclusion These findings suggest a systematically heterogeneous amelioration of symptoms based on a person-centred analysis. Patients with lower depression scores 24h after the first injection are more likely to be in the responder subgroup and to present better symptom relief. Further studies should focus on clinical aspects that might predict this heterogeneity.