Cardiovascular Effects of Combining Subcutaneous or Intravenous Esketamine and the MAO Inhibitor Tranylcypromine for the Treatment of Depression: A Retrospective Cohort Study

Abstract

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 R 2 = 0.11, p = 0.008; DBP: B = 0.21, SE = 0.08, 95% CI 0.06-0.36, p = 0.007; adjusted R 2 = 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.

Comparison of remifentanil and esketamine in combination with propofol for patient sedation during fiberoptic bronchoscopy: a randomized trial

“…In terms of hemodynamics, our results showed that MAP and HR at endotracheal intubation time point in the esketamine group were higher than those in the remifentanil group. However, MAP and HR at endotracheal intubation time decreased signi cantly in remifentanil group compared with administration time, while MAP and HR in esketamine group were stable without signi cant uctuation, which may be related to the cardiovascular excitation effect of esketamine [20]. At the insertion point of bronchoscopy, the elevated level of MAP and HR in remifentanil were signi cantly higher than that in esketamine group, indicating that esketamine provided better circulative stability.…”

Inibidores da monoaminoxidase e cetamina intravenosa: uma associação segura?

“…A única coorte existente até esta data revelou segurança em um número maior de pacientes (n=14) quando comparados ao grupo controle entre pacientes, entretanto, utilizou doses entre 0,25mg/kg e 0,5mg/kg, o que é inferior ao que costuma ocorrer na prática clínica. Ademais, a primeira dose foi administrada por via venosa e as demais por via subcutânea, protocolo divergente dos demonstrados na maioria das evidências [28].…”

The role of ketamine in the treatment of treatment-resistant bipolar depression

“…Σύμφωνα με τουλάχιστον μία μελέτη που έλεγξε τα αποτελέσματα συγχορήγησής του με εσκεταμίνη, διαπιστώθηκε ότι αν και υπήρξαν σημαντικές μεταβολές στην ΑΠ των θεραπευομένων, αυτές δεν ήταν στατιστικά σημαντικές. 45 Κατά συνέπεια η μελλοντική έρευνα μένει να επιβεβαιώσει με ασφάλεια αυτά τα προκαταρκτικά δεδομένα μιας και ορισμένοι αναστολείς της ΜΑΟ εξακολουθούν να χρησιμοποιούνται ακόμη σε ανθεκτικές περιπτώσεις κατάθλιψης.…”