In this meta-analysis, we aimed to estimate and compare the efficacy of add-on treatment of antidepressants with esketamine nasal spray and second-generation antipsychotics in patients with nonpsychotic major depressive disorder and inadequate response to antidepressants. Searching for acute-phase, double-blind, placebo-controlled, randomized trials, we found 22 second-generation antipsychotic (n = 8363) and 3 intranasal esketamine (n = 641) studies. Mean change in the Montgomery Åsberg Depression Rating Scale total score served as outcome. We determined a higher mean difference (vs placebo) for the pooled esketamine nasal spray trials (mean difference = 4.09, 95% confidence interval: 2.01 to 6.17) than for the pooled second-generation antipsychotic augmentation trials (mean difference = 2.05, 95% confidence interval: 1.51 to 2.59). Thus, the effect size for intranasal esketamine was nearly twice as high as those for the second-generation antipsychotics. This indicates high efficacy of add-on esketamine nasal spray in treatment-resistant major depressive disorder compared with other well-established, evidence-based pharmacological options such as augmentation with second-generation antipsychotics.

中文翻译：

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附加 Esketamine 鼻喷雾剂在与附加第二代抗精神病药治疗相关的抵抗性重度抑郁症中的治疗反应。

在这项荟萃分析中，我们旨在评估和比较抗抑郁药与艾氯胺酮鼻喷雾剂和第二代抗精神病药对非精神病性重度抑郁症和抗抑郁药反应不足的患者的附加治疗的疗效。在寻找急性期、双盲、安慰剂对照、随机试验时，我们发现了 22 项第二代抗精神病药（n = 8363）和 3 项鼻内艾氯胺酮（n = 641）研究。蒙哥马利 Åsberg 抑郁量表总分的平均变化作为结果。我们确定了合并艾氯胺酮鼻喷雾试验的平均差异（与安慰剂相比）（平均差异 = 4.09，95% 置信区间：2.01 至 6.17）比合并的第二代抗精神病药物增强试验（平均差异 = 2.05，95%）置信区间：1.51 到 2.59）。因此，鼻内艾氯胺酮的效果几乎是第二代抗精神病药的两倍。这表明，与其他成熟的、基于证据的药理学选择（如使用第二代抗精神病药增强）相比，附加的艾氯胺酮鼻喷雾剂在治疗难治性重度抑郁症中具有较高的疗效。