Anzolin Ana Paula, Goularte Jeferson Ferraz, Pinto Jairo Vinícius, Belmonte-de-Abreu Paulo, Cruz Luciane Nascimento, Cordova Victor Hugo Schaly, Magalhaes Lucas Sueti, Rosa Adriane R, Cereser Keila Maria, Kauer-Sant'Anna Márcia
Graduate Program in Biological Sciences, Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.
Front Psychiatry. 2023 Mar 9;14:1147298. doi: 10.3389/fpsyt.2023.1147298. eCollection 2023.
Psychiatric disorders are associated with more than 90% of reported suicide attempts worldwide, but few treatments have demonstrated a direct effect in reducing suicide risk. Ketamine, originally an anesthetic, has been shown anti-suicide effects in clinical trials designed to treat depression. However, changes at the biochemical level were assessed only in protocols of ketamine with very limited sample sizes, particularly when the subcutaneous route was considered. In addition, the inflammatory changes associated with ketamine effects and their correlation with response to treatment, dose-effect, and suicide risk warrant further investigation. Therefore, we aimed to assess whether ketamine results in better control of suicidal ideation and/or behavior in patients with depressive episodes and whether ketamine affects psychopathology and inflammatory biomarkers.
We report here the design of a naturalistic prospective multicenter study protocol of ketamine in depressive episodes carried out at (HCPA) and (HMV). The study was planned to recruit adult patients with Major depressive disorder (MDD) or Bipolar disorder (BD) types 1 or 2, who are currently in a depressive episode and show symptoms of suicidal ideation and/or behavior according to the Columbia-Suicide Severity Rating Scale (C-SSRS) and have been prescribed ketamine by their assistant psychiatrist. Patients receive ketamine subcutaneously (SC) twice a week for 1 month, but the frequency can be changed or the dose decreased according to the assistant physician's decision. After the last ketamine session, patients are followed-up telephone once a month for up to 6 months. The data will be analyzed using repeated measures statistics to evaluate the reduction in suicide risk as a primary outcome, as per C-SSRS.
We discuss the need for studies with longer follow-ups designed to measure a direct impact on suicide risk and that additional information about the safety and tolerability of ketamine in particular subset of patients such as those with depression and ideation suicide. In line, the mechanism behind the immunomodulatory effects of ketamine is still poorly understood.
https://clinicaltrials.gov/, identifier NCT05249309.
在全球范围内，超过90%的自杀未遂报告与精神疾病有关，但很少有治疗方法能直接降低自杀风险。氯胺酮最初是一种麻醉剂，在治疗抑郁症的临床试验中已显示出抗自杀作用。然而，仅在样本量非常有限的氯胺酮试验方案中评估了生化水平的变化，尤其是考虑皮下给药途径时。此外，与氯胺酮作用相关的炎症变化及其与治疗反应、剂量效应和自杀风险的相关性值得进一步研究。因此，我们旨在评估氯胺酮是否能更好地控制抑郁发作患者的自杀意念和/或行为，以及氯胺酮是否会影响精神病理学和炎症生物标志物。
我们在此报告在[医院名称1]（HCPA）和[医院名称2]（HMV）开展的一项关于氯胺酮治疗抑郁发作的自然前瞻性多中心研究方案的设计。该研究计划招募患有重度抑郁症（MDD）或1型或2型双相情感障碍（BD）的成年患者，这些患者目前处于抑郁发作期，根据哥伦比亚自杀严重程度评定量表（C-SSRS）表现出自杀意念和/或行为症状，并且已由其助理精神科医生开具氯胺酮处方。患者每周皮下注射（SC）氯胺酮两次，持续1个月，但频率可根据助理医生的决定进行更改或剂量减少。在最后一次氯胺酮治疗后，患者每月通过电话随访一次，最长随访6个月。将使用重复测量统计分析数据，以评估作为主要结局的自杀风险降低情况，依据C-SSRS进行评估。
我们讨论了开展随访时间更长的研究的必要性，这些研究旨在衡量对自杀风险的直接影响，以及关于氯胺酮在特定患者亚组（如患有抑郁症和自杀意念的患者）中的安全性和耐受性的更多信息。同样，氯胺酮免疫调节作用背后的机制仍知之甚少。
