Mungo A, Hein M
Hôpital Erasme, Service de Psychiatrie et Laboratoire du Sommeil, Université libre de Bruxelles, ULB, Bruxelles, Belgique.
Hôpital Erasme, Service de Psychiatrie et Laboratoire du Sommeil, Université libre de Bruxelles, ULB, Bruxelles, Belgique.
Encephale. 2022 Aug;48(4):455-461. doi: 10.1016/j.encep.2021.12.002. Epub 2022 Feb 24.
Major depression is a significant public health problem since its lifetime prevalence is estimated at 15-18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment.
A systematic review on the efficacy of esketamine in combination with an SSRI or SNRI for resistant major depressive disorder was performed in July 2021 in the PUBMED database according to the PRISMA criteria. The key words used are: "depressed" [All Fields] OR "depression" [MeSH Terms] OR "depression" [All Fields] OR "depressions" [All Fields] OR "depression s" [All Fields] OR "depressive disorder"[MeSH Terms] OR ("depressive"[All Fields] AND"disorder"[All Fields]) OR"depressive disorder"[All Fields] OR"depressivity"[All Fields] OR"depressive"[All Fields] OR "depressively" [All Fields] OR "depressiveness" [All Fields] OR "depressives" [All Fields]) AND ("esketamine" [Supplementary Concept] OR "esketamine" [All Fields] OR "esketamine" [All Fields]. The inclusion criteria were: efficacy on depressive symptoms of intranasal esketamine combined with an SSRI or an SNRI for major depressive disorder resistant to at least two lines of treatment, RCT and meta-analysis, individual≥18 years, articles in English and French.
Four randomized double-blind studies were selected on the basis of these criteria. The included studies are of grade A and B which leads to a high level of scientific evidence.
Intranasal esketamine in combination with sertraline, escitalopram, duloxetine or venlafaxine prolonged release is more effective than the monotherapy use of these four molecules for the treatment of resistant depression. It has been shown to be effective for a population aged between 18 and 74 years at doses between 28mg and 84mg. Currently, based on these results, intranasal esketamine should be proposed as a second level of treatment after an unsuccessful trial of two antidepressants. It is nevertheless advisable to be careful in its use in a clinical psychiatric population: exclusion of suicidal ideation or antecedent of suicidal acting, absence of psychotic depression, use exclusively for unipolar major depressive disorder. The different conditions of use are also notified in the product characteristics of the European Medicines Agency. Finally, further comparative studies are needed in the future, in the absence of funding from the pharmaceutical company producing esketamine.
重度抑郁症是一个重大的公共卫生问题，其终生患病率估计为15%-18%。其标准治疗基于使用抗抑郁药物，但其有效性有限。事实上，只有三分之二的重度抑郁发作患者在经过两线传统治疗后会达到缓解。在重度抑郁症中，有证据支持神经元谷氨酸能传递存在紊乱。艾氯胺酮似乎通过调节参与这种谷氨酸能神经传递的N-甲基-D-天冬氨酸（NMDA）受体而具有抗抑郁作用。本综述的目的是系统地研究艾氯胺酮联合5-羟色胺再摄取抑制剂（SSRI）或5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）治疗难治性重度抑郁症的疗效。
2021年7月，根据系统评价和Meta分析的首选报告项目（PRISMA）标准，在PubMed数据库中对艾氯胺酮联合SSRI或SNRI治疗难治性重度抑郁症的疗效进行了系统评价。使用的关键词为：“depressed”[所有字段]或“depression”[医学主题词（MeSH）]或“depression”[所有字段]或“depressions”[所有字段]或“depression s”[所有字段]或“depressive disorder”[MeSH]或（“depressive”[所有字段]且“disorder”[所有字段]）或“depressive disorder”[所有字段]或“depressivity”[所有字段]或“depressive”[所有字段]或“depressively”[所有字段]或“depressiveness”[所有字段]或“depressives”[所有字段]）且（“esketamine”[补充概念]或“esketamine”[所有字段]或“esketamine”[所有字段]）。纳入标准为：鼻内艾氯胺酮联合SSRI或SNRI对至少经过两线治疗仍难治的重度抑郁症患者的抑郁症状有效，随机对照试验（RCT）和Meta分析，个体≥18岁，英文和法文文章。
根据这些标准选择了四项随机双盲研究。纳入的研究为A级和B级，这导致了高水平的科学证据。
鼻内艾氯胺酮联合舍曲林、艾司西酞普兰、度洛西汀或缓释文拉法辛治疗难治性抑郁症比单独使用这四种药物更有效。已证明其对年龄在18至74岁之间、剂量在28毫克至84毫克之间的人群有效。目前，基于这些结果，在两种抗抑郁药试验失败后，应将鼻内艾氯胺酮作为二级治疗方案。然而，在临床精神病患者中使用时仍需谨慎：排除自杀意念或自杀行为史，无精神病性抑郁，仅用于单相重度抑郁症。欧洲药品管理局的产品特性中也公布了不同的使用条件。最后，由于生产艾氯胺酮的制药公司未提供资金，未来还需要进一步的比较研究。
