舒拉诺酮及其在治疗重度抑郁症中的作用:综述。

IF 1.1 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Muneeza Ali, Irfan Ullah, Mufaddal Najmuddin Diwan, Alifiya Aamir, Hashir Ali Awan, Abdul Waris Durrani, Qudrat Ullah Qudrat, Sheikh Shoib, Domenico De Berardis
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引用次数: 2

摘要

重度抑郁症(MDD)是一种情绪障碍,被归类为持续两周以上的抑郁情绪和兴趣丧失,并伴有精神疾病诊断与统计手册(DSM-V)诊断标准中列出的一系列症状。重度抑郁症影响全世界约2.64亿人,是最普遍的神经精神疾病。由于假设MDD的病理生理可能是氨基酸神经递质系统异常的结果,包括谷氨酸(主要兴奋性神经递质)和γ-氨基丁酸(GABA), SAGE-217 (Zuranolone)正在被评估为MDD的可能治疗方法。Zuranolone是一种合成的神经活性类固醇(NAS)和GABAA受体的正变构调节剂(PMA),调节GABA的突触和突触外释放。由于其低-中度清除率,每天口服一次,持续2周。HAM-D总分较基线的变化是所有试验的主要终点。一项评估Zuranolone (30mg,每日一次剂量)疗效和安全性的II期试验显示,在第14天,患者的HAM-D总分显著降低,并报告该药耐受性良好,头痛、头晕、恶心和嗜睡是最常见的不良事件(AE)。还进行了额外的III期试验来评估类似的结果,其中期顶线结果已经发布。因此,本文试图简要分析祖拉诺酮的药理学,回顾有关其使用的现有临床数据和结果,并评估其作为一种有效治疗重度抑郁症的前瞻性新疗法的地位。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Zuranolone and its role in treating major depressive disorder: a narrative review.

Major Depressive Disorder (MDD) is a mood disorder classified as a persistent depressive mood and loss of interest lasting for more than two weeks and accompanied by a list of symptoms outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria. MDD affects approximately 264 million people worldwide and is the most prevailing form of neuropsychiatric disorder. Owing to the probable hypothesized pathophysiology of MDD being an outcome of abnormalities in the amino acid neurotransmitter system, including glutamate (the primary excitatory neurotransmitter) and γ-aminobutyric acid (GABA), SAGE-217 (Zuranolone) is being evaluated as a possible therapeutic treatment for MDD. Zuranolone is a synthetic, neuroactive steroid (NAS) and positive allosteric modulator (PMA) of GABAA receptors, regulating both synaptic and extra-synaptic release of GABA. It is administered as a once-daily oral dose for 2 weeks due to its low-moderate clearance. A change in total HAM-D score from baseline was the primary end-point of all the trials. A phase II trial conducted to evaluate the efficacy and safety of Zuranolone (30 mg, once-daily dose), described a significant reduction in total HAM-D score at day 14 and reported the drug to be well tolerated with headache, dizziness, nausea, and somnolence as the most common adverse events (AE). Additional phase III trials were also conducted to evaluate similar outcomes, the interim topline results of which have been released. Consequently, this article attempts to briefly analyze the pharmacology of Zuranolone, review the available clinical data and outcomes regarding its use, and evaluate its place as a prospective novel therapy in the effective management of MDD.

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来源期刊
Hormone Molecular Biology and Clinical Investigation
Hormone Molecular Biology and Clinical Investigation BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.60
自引率
0.00%
发文量
55
期刊介绍: Hormone Molecular Biology and Clinical Investigation (HMBCI) is dedicated to the provision of basic data on molecular aspects of hormones in physiology and pathophysiology. The journal covers the treatment of major diseases, such as endocrine cancers (breast, prostate, endometrium, ovary), renal and lymphoid carcinoma, hypertension, cardiovascular systems, osteoporosis, hormone deficiency in menopause and andropause, obesity, diabetes, brain and related diseases, metabolic syndrome, sexual dysfunction, fetal and pregnancy diseases, as well as the treatment of dysfunctions and deficiencies. HMBCI covers new data on the different steps and factors involved in the mechanism of hormone action. It will equally examine the relation of hormones with the immune system and its environment, as well as new developments in hormone measurements. HMBCI is a blind peer reviewed journal and publishes in English: Original articles, Reviews, Mini Reviews, Short Communications, Case Reports, Letters to the Editor and Opinion papers. Ahead-of-print publishing ensures faster processing of fully proof-read, DOI-citable articles.
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