Włodarczyk Adam, Słupski Jakub, Szarmach Joanna, Cubała Wiesław J
Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Poland.
Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Poland.
Asian J Psychiatr. 2024 Jun;96:104016. doi: 10.1016/j.ajp.2024.104016. Epub 2024 Mar 22.
Ketamine is the prototypal rapid-acting antidepressant (RAAD) for TRD with approved indication for esketamine-nasal spray (ESK-NS). Distinctly, arketamine (R-KET) demonstrates enhanced antidepressant effects and neuroplasticity changes compared to esketamine, with fewer dissociative side effects and abuse potential. This study focuses on R-ketamine's therapeutic implications, safety, and tolerability in TRD treatment.
We report on a year-long follow-up of three TRD patients post-single IV R-KET administration. The study, conducted under the clinical trial PCN-101 (NCT05414422), observed these subjects for healthcare resource utilization and social support system impact. Participants, adults diagnosed with recurrent major depressive disorder without psychotic features, were observed in a year-long follow-up period for safety.
Case analyses revealed significant symptom reduction and improved social and vocational functioning, with reduced sick leaves and hospitalizations post-treatment. However, one case developed a substance use disorder, underscoring the need for vigilant monitoring. The study highlights R-KET's transformative potential in managing depression, indicating a shift in TRD treatment strategies towards early, aggressive interventions.
Despite promising findings, the study faces limitations due to its small sample size, lack of randomization, and potential observational design biases. The results, while aligning with existing ketamine research, require cautious interpretation and warrant further investigation with larger, more robust studies. This exploration of R-KET's role in home-based TRD treatment opens avenues for future research, particularly focusing on its long-term effectiveness and safety in diverse patient populations. This study is registered in clinicaltrials.gov: NCT06232291.
氯胺酮是难治性抑郁症（TRD）的典型速效抗抑郁药（RAAD），艾司氯胺酮鼻喷雾剂（ESK-NS）已获批用于此适应症。明显地，阿氯胺酮（R-KET）与艾司氯胺酮相比，具有更强的抗抑郁作用和神经可塑性变化，且分离性副作用和滥用潜力更少。本研究聚焦于R-氯胺酮在TRD治疗中的治疗意义、安全性和耐受性。
我们报告了3例TRD患者单次静脉注射R-KET后长达一年的随访情况。该研究在临床试验PCN-101（NCT05414422）下进行，观察这些受试者的医疗资源利用情况和社会支持系统影响。参与者为被诊断患有复发性重度抑郁症且无精神病特征的成年人，在长达一年的随访期内观察其安全性。
病例分析显示症状显著减轻，社会和职业功能得到改善，治疗后病假和住院次数减少。然而，有1例出现了物质使用障碍，这凸显了进行警惕监测的必要性。该研究突出了R-KET在治疗抑郁症方面的变革潜力，表明TRD治疗策略正朝着早期、积极干预转变。
尽管有令人鼓舞的发现，但该研究因样本量小、缺乏随机化以及潜在的观察性设计偏差而存在局限性。这些结果虽然与现有的氯胺酮研究一致，但需要谨慎解读，并且有必要通过更大规模、更有力的研究进行进一步调查。对R-KET在居家TRD治疗中作用的这一探索为未来研究开辟了道路，特别是关注其在不同患者群体中的长期有效性和安全性。本研究已在clinicaltrials.gov注册：NCT06232291。
