严重抑郁症(MDD)的广泛范围继续为精神科医生提供有效治疗的挑战。口服抗抑郁药(OAD)改变单胺类神经递质的药物,主要是选择性5-羟色胺再摄取抑制剂(SSRIs)和选择性去甲肾上腺素再摄取抑制剂(SNRIs),几十年来一直是治疗的支柱。虽然这些药物在很大程度上是有益的,相当一部分患者对在适当时间内给予的多种常规疗法没有充分反应,导致诊断为难治性抑郁症(TRD)。氯胺酮,一种非单胺能药物,早就知道静脉内(IV)给药时对TRD的有益作用。在2019年至2020年之间,外消旋氯胺酮的S()对映体的鼻内制剂,艾氯胺酮(ESK),被FDA授予“突破性指定”,并被批准用于表现出急性自杀意图的TRD和MDD患者的适应症。这篇叙述性综述的目的是回顾学术文献并收集临床证据,证实鼻内ESK对其批准的适应症的有效性,同时解决其安全性和耐受性问题。不利影响,以及对认知的影响。概述了这种药物的起源,药理学,并提供标准治疗方案。概述了ESK的双盲随机对照试验(DB-RCTs)的结果,以证明其有效性和安全性数据导致FDA批准。以及其长期的后市场安全结果。然后对ESK和氯胺酮之间的比较试验进行评估,以突出ESK在常规临床实践中作为氯胺酮更实用的替代方案的考虑。作者进一步讨论了目前批准和开发的TRD疗法,提出未来的研究方向,并确定了审查和进一步研究的固有局限性。进行必要的研究,三个数字数据库(PubMed,Medline,和ClinicalTrials.gov)被查询以搜索关键术语,包括氯胺酮,艾氯胺酮,难治性抑郁症,和生物标志物,使用自动化工具和选择性搜索引擎结果。在按标题和摘要精简结果并删除重复项之后,总共选择了37个结果,其中18项是临床试验。蒙哥马利-阿斯伯格抑郁量表(MADRS)评分的降低是大多数临床试验的主要疗效终点。总之,鼻内ESK,当用作市场OADs的辅助时,与单独使用OAD和安慰剂相比,显示出更高的自杀意图治疗TRD和MDD的疗效,并提供了更合适的替代方案。重要的是要注意,需要进一步的研究来充分了解ESK的新作用机制,以及建立TRD的共识定义,这可能有助于更好的检测和治疗方案。需要更集中的定量和定性ESK研究,以及与它在患有精神疾病的患者中的使用有关的那些。
The expansive spectrum of major depressive disorder (MDD) continues to pose challenges for psychiatrists to treat effectively. Oral antidepressant (OAD) medications that alter monoamine neurotransmitters, mainly selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), have been the mainstay of therapy for decades. Although these drugs have been largely beneficial, a considerable subset of patients do not respond adequately to multiple conventional therapies administered for an appropriate length of time, leading to a diagnosis of treatment-resistant depression (TRD). Ketamine, a non-monoaminergic drug, has long been known for its beneficial effects on TRD when given intravenously (IV). Between 2019 and 2020, an intranasal formulation of the S (+) enantiomer of racemic ketamine, esketamine (ESK), was granted \"breakthrough designation\" by the FDA and approved for the indications of TRD and MDD patients exhibiting acute suicidal intent. The objective of this narrative review was to review the academic literature and collect clinical evidence that may corroborate intranasal ESK\'s effectiveness for its approved indications while addressing its safety and tolerability profile, adverse effects, and impact on cognition. An overview of the drug\'s origins, pharmacology, and standard treatment regimen are provided. The outcomes from double-blinded randomized control trials (DB-RCTs) of ESK are outlined to demonstrate the efficacy and safety data leading to its FDA approval, along with its long-term post-market safety outcomes. Comparative trials between ESK and ketamine are then evaluated to highlight ESK\'s consideration as a more practical alternative to ketamine in common clinical practice. The authors further discuss currently approved and developing therapies for TRD, propose future research directions, and identify the inherent limitations of the review and further research. To conduct the research required, three digital databases (PubMed, Medline, and ClinicalTrials.gov) were queried to search for key terms, including ketamine, esketamine, treatment-resistant depression, and biomarkers, using automation tools along with selective search engine results. After streamlining the results by title and abstract and removing duplicates, a total of 37 results were chosen, of which 18 are clinical trials. A reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score was the primary efficacy endpoint for most of these clinical trials. In conclusion, intranasal ESK, when used as an adjunct to market OADs, shows greater efficacy in treating TRD and MDD with suicidal intent compared to OADs and placebo alone and provides a more suitable alternative to IV ketamine. It is important to note that further research is required to fully understand the novel mechanism of action of ESK, as well as the establishment of a consensus definition of TRD, which may facilitate better detection and treatment protocols. More focused quantitative and qualitative ESK studies are needed, as well as those pertaining to its use in patients with co-existing mental illnesses.