Cardiovascular Effects of Combining Subcutaneous or Intravenous Esketamine and the MAO Inhibitor Tranylcypromine for the Treatment of Depression: A Retrospective Cohort Study
Vera Miriam Ludwig, Cathrin Sauer, Allan H. Young, James Rucker, Michael Bauer, Hannelore Findeis, Philipp Ritter
CNS Drugs July 20, 2021 DOI: 10.1007/s40263-021-00837-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective cohort study Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Inpatients treated for severe depression in unipolar, bipolar, and schizoaffective disorder |
| Interventions | Esketamine Tranylcypromine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Tranylcypromine Psychopharmacology Retrospective cohort study Depression economics Neurology Monoamine oxidase inhibitor Anesthesia Pharmacotherapy |
| Citations | 23 |
| Key findings | Combining esketamine with tranylcypromine produces statistically significant but clinically insignificant blood pressure changes, indicating safety at standard doses. |
Abstract
(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.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 8
- Use of ketamine for treatment resistant depression: updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada. Frontiers in Psychiatry 2023
- Effect of low-dose esketamine on postoperative quality of recovery in total laparoscopic hysterectomy: a randomized controlled trial. Perioperative medicine (London, England) July 23, 2025
- Optimizing real-world benefit and risk of new psychedelic medications: the need for innovative postmarket surveillance Nature Mental Health May 1, 2024
- Effects of Esketamine Versus Remifentanil on Hemodynamics and Prognosis in Patients with Septic Shock Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial. Drug Design, Development and Therapy 2025
- Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data. CNS Drugs January 17, 2026
and 3 more in the library
Cites 11
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
and 6 more in the library