Background

(Es)ketamine and monoamine oxidase inhibitors (MAOIs), e.g., tranylcypromine, are therapeutic options for treatment-resistant major depression. Simultaneous administration is currently not recommended because of concern about hypertensive crises.

Objective

Our objective was to evaluate whether changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) during esketamine administration differed between patients who concomitantly received tranylcypromine and those who did not.

Methods

This was a retrospective cohort study utilizing cardiovascular monitoring data from inpatients treated for severe depression in unipolar, bipolar, and schizoaffective disorder. Primary outcomes were change in mean BP and HR during the first hour after intravenous or subcutaneous esketamine administration compared with baseline, controlled for confounders. Secondary analyses quantify differences in absolute BP during esketamine treatment and comparisons of BP peaks, temporal effects, and intraindividual comparisons before and after tranylcypromine initiation.

Results

Our analysis included 509 esketamine administrations in 43 patients, 14 of whom concomitantly received tranylcypromine. Controlling for creatinine and age, mean ± standard deviation (SD) BP changes were significantly increased by concomitant tranylcypromine treatment (ΔSBP: F[1,503] = 86.73, p < 0.001; ΔDBP: F[1,503] = 55.71, p < 0.001), but HR remained unaffected. Mean SBP change during esketamine administration was 2.96 ± 18.11 mmHg in patients receiving tranylcypromine (TCP+) and −8.84 ± 11.31 mmHg in those who did not (TCP−). Changes in DBP were −2.81 ± 11.20 mmHg for TCP+ and −10.77 ± 9.13 mmHg for TCP−. Moreover, we found a significant dose–response relationship between tranylcypromine dose and BP (SBP: B = 0.35, standard error [SE] = 0.12, 95% confidence interval [CI] 0.12–0.60, p = 0.004; adjusted R² = 0.11, p = 0.008; DBP: B = 0.21, SE = 0.08, 95% CI 0.06–0.36, p = 0.007; adjusted R² = 0.08; p = 0.023).

Conclusions

Although statistically significant changes in BP were identified in patients receiving tranylcypromine and esketamine, these changes were clinically insignificant. Thus, combining esketamine and this MAOI appears to be safe at standard doses. The dose–response relationship calls for caution with higher doses of tranylcypromine.

中文翻译：

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联合皮下或静脉注射艾司氯胺酮和 MAO 抑制剂反苯环丙胺治疗抑郁症的心血管作用：一项回顾性队列研究

背景

(Es) 氯胺酮和单胺氧化酶抑制剂 (MAOIs)，例如反苯环丙胺，是难治性重性抑郁症的治疗选择。由于担心高血压危象，目前不推荐同时给药。

客观的

我们的目标是评估同时接受反苯环丙胺和未接受艾氯胺酮的患者在使用艾氯胺酮期间收缩压 (SBP)、舒张压 (DBP) 和心率 (HR) 的变化是否存在差异。

方法

这是一项回顾性队列研究，利用单相、双相和分裂情感障碍严重抑郁症住院患者的心血管监测数据。主要结果是与基线相比，静脉内或皮下注射艾氯胺酮后第一个小时内平均 BP 和 HR 的变化，控制了混杂因素。二次分析量化了 esketamine 治疗期间绝对 BP 的差异，并比较了反苯环丙胺开始前后的 BP 峰值、时间效应和个体内比较。

结果

我们的分析包括 43 名患者的 509 次艾氯胺酮给药，其中 14 人同时接受反苯环丙胺。控制肌酐和年龄，均值 ± 标准差 (SD) BP 变化通过伴随反苯环丙胺治疗显着增加（ΔSBP：F [1,503] = 86.73，p  < 0.001；ΔDBP：F [1,503] = 55.71，p  < 0.001），但 HR 不受影响。在接受反苯环丙胺 (TCP+) 的患者中，艾氯胺酮给药期间的平均 SBP 变化为 2.96 ± 18.11 mmHg，而在未接受 (TCP-) 的患者中，平均 SBP 变化为 -8.84 ± 11.31 mmHg。TCP+ 的 DBP 变化为 -2.81 ± 11.20 mmHg，TCP- 的变化为 -10.77 ± 9.13 mmHg。此外，我们发现反苯环丙胺剂量与 BP 之间存在显着的剂量反应关系（SBP：B = 0.35，标准误差 [SE] = 0.12，95% 置信区间 [CI] 0.12–0.60，p  = 0.004；调整后的R ²  = 0.11，p  = 0.008；DBP：B  = 0.21，SE = 0.08，95% CI 0.06–0.36，p  = 0.007；调整后的R ²  = 0.08；p  = 0.023)。

结论

尽管在接受反苯环丙胺和艾氯胺酮的患者中发现了具有统计学意义的血压变化，但这些变化在临床上并不显着。因此，在标准剂量下，将艾氯胺酮和这种 MAOI 结合起来似乎是安全的。剂量反应关系需要谨慎使用较高剂量的反苯环丙胺。