Abstract：
In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD.
摘要：
在ESCAPE-TRD(NCT04338321)中,与喹硫平缓释剂（XR）相比，在难治性抑郁症（TRD）患者中，艾氯胺酮鼻喷雾剂（NS）显着增加了第8周缓解的可能性，以及在第8周缓解后第32周无复发的可能性。这里,我们探索时间进程，IIIb期ESCAPE-TRD试验中治疗紧急不良事件(TEAE)的负担和后果。TRD患者以1:1的比例随机分配给艾氯胺酮NS或喹硫平XR，与正在进行的选择性5-羟色胺再摄取抑制剂/5-羟色胺去甲肾上腺素再摄取抑制剂一起按标签给药。在这个二级出版物中，安全性分析(包括接受≥1剂量研究治疗的患者)包括发病率,TEAE的严重程度和持续时间(Kaplan-Meier方法)，以及随后的性格变化。P值未针对多次测试进行调整。336名患者被随机分配给艾氯胺酮NS和340名患者接受喹硫平XR;334和336名患者接受≥1剂量的研究治疗。分别。与喹硫平XR相比，esketamineNS的TEAE明显更常见（91.9％对78.0％；p<0.001），但通常是轻度/中度和短暂的性质：在同一天解决的比例更大（92.0％对12.1％），导致治疗中断的患者明显减少（4.2％对11.0％，分别为；p<0.001)。使用esketamineNS治疗TEAE的天数比例显著低于喹硫平XR(中位数：11.9%对21.3%;p<0.001)。虽然使用esketamineNS更频繁，TEAE通常是短暂的和轻度的，与喹硫平XR相比，停药的可能性较小。数据与已建立的安全概况一致，没有发现新的安全信号。除了更高的疗效，与喹硫平XR相比,艾氯胺酮NS明显更有利的耐受性特征进一步支持其用于TRD.
