Roncero Carlos, Merizalde-Torres Milton, Szerman Néstor, Torrens Marta, Vega Pablo, Andres-Olivera Pilar, Javier Álvarez Francisco
Health Science Faculty, European University Miguel de Cervantes (UEMC), C/Padre Julio Chevalier, 2, 47012, Valladolid, Spain.
Psychiatry Unit, School of Medicine, University of Salamanca, Salamanca, Spain.
Ther Adv Drug Saf. 2025 Jan 29;16:20420986241310685. doi: 10.1177/20420986241310685. eCollection 2025.
In 2019, intranasal esketamine gained approval as a promising therapy for those individuals grappling with treatment-resistant depression. Both clinical trials and real-world studies have underscored its efficacy in alleviating and remitting depressive symptoms, with sustained benefits observed for nearly 4.5 years. As the -enantiomer of ketamine, esketamine's dosing guidelines and strict medical supervision stem from prior research on ketamine's use in depression and history as a recreational drug. Despite initial concerns, long-term clinical studies have not documented instances of abuse, misuse, addiction or withdrawal, and the same was found in case reports or subsamples of high-risk populations with comorbidities such as substance use disorder or alcohol use disorder. Esketamine has proven to be safe and well tolerated without fostering new-onset substance use in vulnerable groups. Real-world studies reinforced these observations, reporting no adverse events (AEs) related to pharmacological interactions of esketamine with any other substance, and no new-onset drug or alcohol misuse, craving, misuse or diversion of use. Reports of esketamine craving remain rare, with only one case report documented in 2022. Most drug-related AEs reported in pharmacovigilance databases are those identified in the product's technical data sheet and with known reported frequency. More importantly, no register of illicit acquisition of esketamine or its tampering for obtaining ketamine or other altered products was found in our search. Overall, our review confirms esketamine's safety across diverse patient populations, reassuring its responsible use and the scarcity of reports of abuse or misuse since its introduction to the market.
2019年，鼻内用艾氯胺酮获批成为治疗难治性抑郁症患者的一种有前景的疗法。临床试验和真实世界研究均强调了其在缓解和减轻抑郁症状方面的疗效，且观察到近4.5年的持续益处。作为氯胺酮的左旋对映体，艾氯胺酮的给药指南和严格的医学监管源于此前关于氯胺酮用于抑郁症治疗的研究以及其作为娱乐性药物的历史。尽管最初存在担忧，但长期临床研究并未记录到滥用、误用、成瘾或戒断的情况，在有物质使用障碍或酒精使用障碍等合并症的高危人群的病例报告或子样本中也未发现此类情况。事实证明，艾氯胺酮安全且耐受性良好，不会在弱势群体中引发新的物质使用问题。真实世界研究强化了这些观察结果，报告称没有与艾氯胺酮与任何其他物质的药物相互作用相关的不良事件（AE），也没有新的药物或酒精滥用、渴望、误用或使用转移情况。关于艾氯胺酮渴望的报告仍然很少，2022年仅有一例病例报告。药物警戒数据库中报告的大多数与药物相关的不良事件是产品技术数据表中已确定的且有已知报告频率的事件。更重要的是，在我们的搜索中未发现非法获取艾氯胺酮或对其进行篡改以获取氯胺酮或其他改变产品的记录。总体而言，我们的综述证实了艾氯胺酮在不同患者群体中的安全性，这使其合理使用令人安心，且自上市以来关于滥用或误用的报告很少。
