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Gender Differences in Suicidal and Self-Harming Responses to Esketamine: A Real-World Retrospective Study
Vassilis Martiadis1, Fabiola Raffone1, Danilo Atripaldi2
1Community Mental Health Center DS 25, Department of Mental Health, Asl Napoli 1 Centro, Naples, Italy.
Introduction:
Treatment-resistant depression (TRD) is a severe psychiatric condition that may increase the risk of suicidal thoughts and self-harming behaviors. Intranasal esketamine has emerged as an effective treatment for TRD, also addressing depression-related emergencies such as suicidal ideation.
Methods:
This retrospective observational study analyzed 26 outpatients with TRD treated with adjunctive intranasal esketamine alongside ongoing oral antidepressants for 4 weeks. Suicidal ideation and behaviors were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), and depressive symptoms were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, week 2, and week 4. Statistical analyses included repeated-measures ANOVA and subgroup analyses by gender and baseline self-harm profile.
Results:
Esketamine significantly reduced suicidal ideation and depressive symptoms from baseline to week 2 and week 4 (all p<.001). Additionally, non-suicidal self-harm declined, exhibiting genderspecific patterns: women demonstrated a faster reduction in non-suicidal self-harm, whereas men showed slower improvement in suicidal self-harm. A strong correlation between depressive symptoms and suicidality confirmed their interplay.
Discussion:
In our real-world TRD sample, adjunctive intranasal esketamine led to a rapid and sustained reduction in suicidality and depressive symptoms, with distinct gender-related patterns in self-harm trajectories. These findings may inform individualized monitoring strategies. Limitations include the small sample size, retrospective design, and lack of a control group.
Conclusion:
Esketamine rapidly improved suicidality and depression in TRD, with preliminary evidence suggesting gender-specific responses, and highlighting the importance of tailored interventions to maximize outcomes. Further research is needed to confirm these differences, explore the long-term effects, and understand the underlying mechanisms.
