Key result
Tranylcypromine with esketamine is linked to a clinically minor ~12-mmHg difference in SBP.
Why the study?
Simultaneous administration of esketamine and the MAOI tranylcypromine is currently not recommended due to concerns about hypertensive crises, but cardiovascular effects have not been quantitatively compared.
Cohort (n=43)
No
Suggests combining these therapies may be hemodynamically tolerable despite current contraindications; leaves open the.
(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. 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. 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. 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). 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.
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Ludwig et al. (2021) conducted a cohort in Major depressive episode (n=43). Concomitant tranylcypromine vs. Esketamine without tranylcypromine was evaluated on Change in mean systolic blood pressure (ΔSBP) from baseline during the first hour after esketamine administration (p=<0.001). Concomitant tranylcypromine during esketamine administration led to clinically insignificant changes in systolic blood pressure (2.96 vs -8.84 mmHg; p<0.001), suggesting safety at standard doses.
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