Efficacy of intravenous esketamine in reducing suicidal ideation and major depressive symptoms: A real-world evidence study

Intravenous esketamine treatment (EKIT) has been proposed to have greater efficacy than its racemic counterpart for the management of treatment-resistant depression and suicidal ideation; however, few studies have been documented this regard. We evaluated the clinical evolution of treatment-resistant major depressive disorder (MDD) and bipolar affective disorder (BAD) with or without suicidal ideation in patients who received EKIT, based on real-world data. This study included patients with treatment-resistant MDD/BAD primary diagnosed by their own psychiatrists and prescribed EKIT. In the Cetamine Clinic, primary and follow-up measurements used Patient Health Questionnaire (PHQ-9). The study analyzed 263 patients with baseline PHQ-9>4 who received at least two infusions of EKIT. After the EKIT induction phase, PHQ-9 score reduced from 20.5±4.6 to 9.8±7.0 (p<0.001; Cohen's d = 1.47). Based on the final PHQ-9 score, 26.2%, 32.7%, 19.4%, and 21.7% of the patients achieved remission (PHQ-9≤4), had a good-response (PHQ-9 reduction >50%), had a mild-response (PHQ-9 reduction 25-50%) and failed, respectively. Among 92 patients at high risk of suicide at baseline (PHQ-9 item-9=3), 84% became low-risk after EKIT. The retrospective design of the study, diagnosis of treatment-resistant MDD/BAD by the concerned psychiatrists, and lack of washout for any medication possibly contributed to a heterogeneous study population. However, these characteristics were attributed to the real-world design. Monitoring was exclusively conducted using the PHQ-9 and long-term follow-up was not performed. Our findings demonstrated a robust overall response regarding depression after EKIT; moreover, a substantial proportion of the participants demonstrated a mild response. A notable response concerning suicide was observed after EKIT.