Cardiovascular Effects of Non-Selective Monoamine Oxidase Inhibitors and Intranasal Esketamine Combination in Depression - A Quasi-Experimental Design with Bayesian Analyses.

Ketamine and esketamine, when used alongside non-selective monoamine oxidase inhibitors, do not cause clinically significant increases in blood pressure or heart rate. In 193 esketamine sessions with 13 patients, systolic pressure rose by 8.68 mmHg, diastolic by 6.57 mmHg, and heart rate by 3.5 beats per minute—changes not considered clinically meaningful. The combination of esketamine with monoamine oxidase inhibitors was not linked to elevated blood pressure. These results suggest minimal risk of sympathomimetic synergy with this drug combination, supporting its safe use in treatment-resistant depression.

Study at a glance

Abstract

Ketamine and esketamine (ESK) offer new treatment options for resistant depression. Unlike traditional antidepressants, they can be used in combination with non-selective monoamine oxidase inhibitors (NS-MAOI) without the risk of serotonergic syndrome. However, potential sympathomimetic synergy may lead to elevated blood pressure (BP). This series investigates whether cardiovascular parameters (heart rate, systolic [SP], and diastolic [DP] pressures) increase during ESK sessions and whether the ESK+NS-MAOI combination is associated with BP elevations.We collected cardiovascular parameters for ESK sessions conducted between 2018 and 2022. These parameters were measured at baseline and every 30 min for 2 h. Patients were categorized into two non-equivalent groups: those receiving ESK alone and those receiving ESK+NS-MAOI. A Bayesian random model was used to estimate the evolution of these parameters, while a Bayesian hierarchical model assessed factors contributing to BP elevation.ESK sessions (n=193), of which 116 involved NS-MAOI, were performed in 13 patients. SP, DP, and heart rate showed peak increases during sessions, but these changes were not clinically significant (SP+8.68 mmHg, DP+6.57 mmHg, and heart rate+3.5 bpm). No significant differences were found between the ESK-alone and ESK+NS-MAOI groups. The combination was not identified as a factor linked to BP elevations.These findings align with previous research on ketamine derivatives and suggest minimal peripheric sympathomimetic synergy with NS-MAOI. Bayesian models were used to account for biases intrinsically related to these ecological data and provide a foundation for future open adversarial collaborations. Registration NCT05530668.