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

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.