How the Food and Drug Administration Drug Approval Process Relates to the Potential Approval of Intravenous Racemic Ketamine for Treatment-resistant Major Depression.

IF 1.3 4区 医学 Q3 PSYCHIATRY
Sheldon H Preskorn
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Abstract

This column focuses on the status of intravenous racemic ketamine for the treatment of patients suffering from a form of major depressive disorder that does not respond to trials of currently available biogenic amine antidepressants. To provide context, the column reviews the 3 pivotal elements of the usual Food and Drug Administration (FDA) drug approval process: (1) the unmet medical need (ie, the indication) for which the drug is being developed, (2) the efficacy of the drug for that condition, and (3) the safety/tolerability of the drug. This column is based on the author's 45-year history of drug development work and is not a statement of the FDA. There are typically 3 phases in the drug development process: (1) studies done in normal volunteers, (2) typically small-scale proof of concept studies, and (3) large-scale registration trials. This third phase is critical in determining the efficacy, safety, and tolerability of the drug in a manner that most closely follows the clinical use of the drug. This column focuses specifically on whether generally small-scale studies done in academic centers are sufficient for drug approval, and it briefly reviews lithium and clozapine as examples of psychiatric medications that had such academic research in the literature, as well as clinical use in other countries. Those data supported the unique value of these medications in patients with bipolar disorder and treatment-resistant schizophrenia (ie, the unmet medical need), respectively, and the findings led American psychiatrists to advocate for FDA approval of these medications. Their efforts led to the needed registration trials for FDA approval of these medications. This column reviews the key features of registration trials and the reason that they are critical for FDA approval, and it discusses 2 special considerations related to the intravenous administration of racemic ketamine. First, racemic ketamine is not esketamine but, instead, it contains R-ketamine in addition to S-ketamine (ie, esketamine). The second consideration is that differences between intravenous and intranasal administration may affect the safety of the drug. While safety concerns were specifically addressed in the registration trials for esketamine, comparable research remains to be done for intravenous racemic ketamine. Understanding how the FDA's drug approval process works is important for prescribers, their patients, and the public.

美国食品和药物管理局的药物审批程序如何与可能批准静脉注射消旋氯胺酮治疗耐药性重度抑郁症相关联。
本专栏主要介绍静脉注射外消旋氯胺酮治疗重度抑郁症患者的情况,这种患者对目前可用的生物胺类抗抑郁药试验无反应。为了提供背景资料,本专栏回顾了美国食品和药物管理局(FDA)通常药物审批程序的三个关键要素:(1)正在开发的药物尚未满足的医疗需求(即适应症);(2)药物对该病症的疗效;以及(3)药物的安全性/耐受性。本专栏基于作者 45 年的药物开发工作经验,并非 FDA 的声明。药物开发过程通常分为 3 个阶段:(1)在正常志愿者中进行的研究;(2)典型的小规模概念验证研究;(3)大规模注册试验。第三阶段对于以最贴近临床用药的方式确定药物的疗效、安全性和耐受性至关重要。本专栏特别关注在学术中心进行的一般小规模研究是否足以作为药物审批的依据,并简要回顾了锂和氯氮平作为精神科药物的例子,这些药物在文献中进行了此类学术研究,并在其他国家进行了临床使用。这些数据分别支持了这些药物在双相情感障碍和耐药性精神分裂症患者中的独特价值(即未满足的医疗需求),这些研究结果促使美国精神科医生倡导美国食品药物管理局批准这些药物。他们的努力促成了 FDA 批准这些药物所需的注册试验。本专栏回顾了注册试验的主要特点以及注册试验对 FDA 批准至关重要的原因,并讨论了与外消旋氯胺酮静脉注射有关的两个特殊注意事项。首先,外消旋氯胺酮不是艾司氯胺酮,而是除了 S-氯胺酮(即艾司氯胺酮)外还含有 R-氯胺酮。第二个考虑因素是静脉注射和鼻内注射的不同可能会影响药物的安全性。虽然在埃斯氯胺酮的注册试验中专门讨论了安全性问题,但对于静脉注射外消旋氯胺酮仍有待进行类似的研究。了解美国食品和药物管理局的药物审批程序对处方者、患者和公众都很重要。
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来源期刊
CiteScore
2.30
自引率
10.50%
发文量
159
审稿时长
>12 weeks
期刊介绍: Journal of Psychiatric Practice® seizes the day with its emphasis on the three Rs — readability, reliability, and relevance. Featuring an eye-catching style, the journal combines clinically applicable reviews, case studies, and articles on treatment advances with practical and informative tips for treating patients. Mental health professionals will want access to this review journal — for sharpening their clinical skills, discovering the best in treatment, and navigating this rapidly changing field. Journal of Psychiatric Practice combines clinically applicable reviews, case studies, and articles on treatment advances with informative "how to" tips for surviving in a managed care environment.
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