Psychiatric Department, Azienda Socio Sanitaria Territoriale Monza, via G.B. Pergolesi 33, 20900 Monza, Italy.
Department of Medicine and Surgery, University of Milano Bicocca, via Cadore 38, 20900 Monza, Italy.
Int J Mol Sci. 2021 Aug 28;22(17):9338. doi: 10.3390/ijms22179338.
Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.
依他佐辛（ESK）已被批准为治疗抵抗性抑郁症（TRD）的快速起效鼻腔治疗药物。尽管现有研究已经调查了 ESK 在 4 周诱导期的疗效，但我们对 ESK 的长期疗效知之甚少。本系统评价的目的是总结现有关于 ESK 治疗 TRD 的长期疗效数据。进行了一项系统搜索，包括截至 2021 年 3 月 31 日的英文文章。搜索发现了 7 项相关研究，涉及 1024 名成年 TRD 患者。在 4 周诱导期后继续使用 ESK 治疗可能与 TRD 患者预防复发的稳定疗效有关。相反，ESK 停药后的长期抗抑郁效果可能有限，尽管三项研究的数据存在中至高偏倚风险。总体而言，该化合物在长期应用中的疗效结果喜忧参半。根据我们的研究结果，ESK 治疗应在诱导期后继续进行，以达到预防复发的稳定疗效，而 ESK 停药后的长期抗抑郁和抗自杀作用则不一致。目前，ESK 治疗长期 TRD 的疗效证据水平仍然较低，需要更多的 RCT 研究，样本量更大，并采用活性对照。
