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

TY - JOUR

T1 - Cardiovascular Effects of Combining Subcutaneous or Intravenous Esketamine and the MAO Inhibitor Tranylcypromine for the Treatment of Depression

T2 - A Retrospective Cohort Study

AU - Ludwig, Vera M

AU - Sauer, Cathrin

AU - Young, Allan H

AU - Rucker, James

AU - Bauer, Michael

AU - Findeis, Hannelore

AU - Ritter, Philipp

N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. This report represents independent research supported by Bundesministerium für Bildung und Forschung (BMBF) grant tC2020_03_MED (transCampus/TUD/BMBF), as well as the National Institute for Health Research (AHY and NIHR Clinician Scientist Award JR CS-2017-17- 007) and NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. PR received grants from the BMBF. The views expressed are those of the author(s) and not necessarily those of the BMBF, NHS, NIHR, or the Department of Health. Funding Information: AHY gave paid lectures and is on advisory boards for the following companies: AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, LivaNova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, and COMPASS and serves as a consultant to Johnson & Johnson and LivaNova. JR was paid by COMPASS Pathways to attend trial-related meetings and conferences to present the results of research using psilocybin and served as a paid consultant to Beckley PsyTech and Clerkenwell Health. MB has received institutional funding/grant support from Deutsche Forschungsgemeinschaft (DFG), BMBF, and the European Commission; has received speaker honoraria and/or travel compensation from Aristo, Hexal AG, Janssen Pharmaceutica NV, Janssen-Cilag, and Sunovion; has served on advisory boards or received honoraria consultancy from GH Research, Janssen-Cilag, neuraxpharm, Novartis, Sandoz, Shire International GmbH, Sumitomo Dainippon, Sunovion, and Takeda. The authors assert that the mentioned companies had no influence over the content of this article. VML, CS, HF, and PR have no conflicts of interest that are directly relevant to the content of this article. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85110799258&partnerID=8YFLogxK

U2 - 10.1007/s40263-021-00837-6

DO - 10.1007/s40263-021-00837-6

M3 - Article

C2 - 34283390

SN - 1172-7047

VL - 35

SP - 881

EP - 892

JO - CNS Drugs

JF - CNS Drugs

IS - 8

ER -