Hôpitaux universitaires de Marseille, Service de pharmacologie clinique, Centre d'évaluation et d'information sur la pharmacodépendance - Addictovigilance, Marseille, France.
Aix-Marseille Université, Inserm, UMR 1106, Marseille, France.
Fundam Clin Pharmacol. 2022 Jun;36(3):572-581. doi: 10.1111/fcp.12745. Epub 2021 Dec 23.
Prominent features of esketamine (e.g., similar mechanism of action as ketamine and target population) require to be vigilant regarding its benefits/risks balance and its risks of abuse in real-life settings. The aim of this study was to review all available pharmacological and clinical data to assess the abuse potential of esketamine shortly after its marketing. This multidimensional study is a quantitative and qualitative analysis of complementary data sources, ranging from preauthorization data (i.e., fundamental pharmacology and clinical trials) to real-life settings data (i.e., pharmacovigilance databases and web forums). According to esketamine pharmacology, its psychoactive effects play a role both in its therapeutic effect and its abuse potential. Only one out of the three short-term efficacy trials found a significant difference between esketamine and placebo in treatment-resistant depression. Beside adverse events that may be sought for abuse purpose (e.g., dissociation, sedation, euphoric mood, hallucination, feeling drunk, and derealization), clinical signs related to substance use disorder (e.g., tolerance, withdrawal syndrome, and drug dependence) and misuse (e.g., off-label use) were also identified in pharmacovigilance databases. Analysis of pharmacovigilance narratives and web forums showed that esketamine psychoactive effects are appreciated by some patients, while they are badly experienced by others. Strict compliance with the market authorization, close monitoring of patients by psychiatrists, and surveillance of any signs of misuse, abuse, or dependence must be part of any treatment course.
依他佐辛（例如，与氯胺酮相似的作用机制和目标人群）的突出特点要求警惕其获益/风险平衡，并警惕其在现实环境中被滥用的风险。本研究旨在综述所有可用的药理学和临床数据，以评估依他佐辛上市后不久的滥用潜力。这项多维研究是对互补数据源的定量和定性分析，范围从授权前数据（即基本药理学和临床试验）到现实环境数据（即药物警戒数据库和网络论坛）。根据依他佐辛药理学，其精神活性作用在其治疗效果和滥用潜力中均发挥作用。仅在三项短期疗效试验中有一项发现依他佐辛与安慰剂在治疗抵抗性抑郁症方面有显著差异。除了可能因滥用目的而寻求的不良事件（例如分离、镇静、欣快情绪、幻觉、醉酒感和现实感丧失）之外，药物警戒数据库中还确定了与物质使用障碍（例如耐受、戒断综合征和药物依赖）和误用（例如标签外使用）相关的临床体征。药物警戒叙述和网络论坛分析表明，一些患者对依他佐辛的精神活性作用表示赞赏，而另一些患者则对此表示反感。必须严格遵守市场授权，由精神科医生密切监测患者，并监测任何滥用、误用或依赖的迹象，这必须成为任何治疗过程的一部分。
