PRODAF-Programa de Transtornos Afetivos, Department of Psychiatry, Federal University of Sao Paulo, Rua Major Maragliano, 241, Vila Mariana, Sao Paulo, SP, 04017-030, Brazil.
CNS Unit, BR Trials, Sao Paulo, Brazil.
Clin Drug Investig. 2022 Oct;42(10):865-873. doi: 10.1007/s40261-022-01193-z. Epub 2022 Aug 31.
Affective disorders account for most cases of suicide. The pharmacological arsenal to treat suicidality is limited and available agents take too long to take effect. A large body of evidence shows optimal results of ketamine for treating depression, but the evidence concerning suicidality has not been fully described. We report the first real-world study of severely depressed patients presenting with suicide ideation who were treated with repeated administration of subcutaneous esketamine.
We analyzed data from 70 acutely depressed subjects diagnosed with resistant major depressive disorder or bipolar depression. Subjects were administered subcutaneous esketamine once a week for 6 weeks. The primary efficacy endpoint, the change from baseline to 24-h post-administration 6 in the item 10 Montgomery-Åsberg Depression Rating Scale score, was analyzed using a mixed-effects repeated-measures model.
There were significant effects for time on item 10 Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001) but not for a time × diagnosis interaction (p = 0.164) from baseline to the end of the study. Efficacy of esketamine did not differ between groups (major depressive disorder vs bipolar depression) at any timepoint. Statistical significance on suicidality scores was observed from 24 h after the first administration (p < 0.001), and a further reduction was observed with repeated administrations. Esketamine was safe and well tolerated. Mean heart rate remained stable during the administrations and the blood pressure increase was self-limited.
Repeated subcutaneous esketamine administration had significant anti-suicidality effects in both major depressive disorder and bipolar groups, with a rapid onset of action and a good tolerability profile. Large randomized controlled trials are warranted to confirm these preliminary findings.
情感障碍占自杀病例的大多数。用于治疗自杀意念的药物 arsenal 有限，且现有药物起效时间过长。大量证据表明氯胺酮治疗抑郁症的效果最佳，但有关自杀意念的证据尚未充分描述。我们报告了首例使用重复皮下给予氯胺酮治疗有自杀意念的重度抑郁症患者的真实世界研究。
我们分析了 70 名患有难治性重度抑郁症或双相情感障碍的急性抑郁症患者的数据。患者每周接受一次皮下氯胺酮治疗，共 6 周。主要疗效终点是在第 6 次给药后 24 小时内，10 项蒙哥马利-阿斯伯格抑郁评定量表（Montgomery-Åsberg Depression Rating Scale）的第 10 项得分较基线的变化，采用混合效应重复测量模型进行分析。
从基线到研究结束，时间对第 10 项蒙哥马利-阿斯伯格抑郁评定量表评分的影响有统计学意义（p<0.0001），但时间与诊断的交互作用无统计学意义（p=0.164）。氯胺酮的疗效在任何时间点均未在重度抑郁症组和双相情感障碍组之间存在差异。在第一次给药后 24 小时（p<0.001）开始观察到自杀评分有统计学意义的改善，并且随着重复给药进一步降低。氯胺酮安全且耐受良好。给药期间平均心率保持稳定，血压升高呈自限性。
重复皮下给予氯胺酮对重度抑郁症和双相情感障碍组均具有显著的抗自杀意念作用，起效迅速，耐受性良好。需要进行大型随机对照试验来证实这些初步发现。
