Journal Article

Concomitant Administration of Ozanimod and Serotonergic Antidepressants in Patients With Ulcerative Colitis or Relapsing Multiple Sclerosis

Horst, Sara, Wu, Hsiuanlin, Petersen, AnnKatrin, Regueiro, Miguel, Lawlor, Garrett, Siegmund, Britta, Moslin, Ryan, Fischer, Monika, D’Haens, Geert, Charles, Lorna, Tatosian, Daniel, Colombel, Jean-Frederic

2025

Overview

Abstract Background Ozanimod, approved for the treatment of moderately to severely active ulcerative colitis (UC) and relapsing multiple sclerosis (RMS), is a weak in vitro monoamine oxidase B (MAO-B) inhibitor. MAO-B inhibitors can cause serotonin accumulation with concomitant use of selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs). We evaluated the incidence of treatment-emergent adverse events (TEAEs) potentially associated with serotonin accumulation during ozanimod and concomitant SSRI/SNRI use in this post hoc analysis of pooled UC studies and the open-label extension RMS DAYBREAK. Methods Data for ozanimod 0.92 mg from pooled UC studies (n = 1158; cutoff: January 10, 2022) and RMS DAYBREAK (n = 2257; cutoff: February 1, 2022) were analyzed. Concomitant SSRI/SNRI use was allowed in the UC (n = 67) and RMS (n = 274) studies. A narrow Medical Dictionary for Regulatory Activities search (“serotonin syndrome,” “neuroleptic malignant syndrome,” and “malignant hyperthermia”) and a broad search including terms potentially associated with serotonin accumulation were conducted. The percentages of patients with TEAEs in both searches were analyzed by concomitant SSRI/SNRI use when the TEAE occurred. Results No patients had TEAEs matching the narrow search criteria. No differences were observed in the percentages of patients with ≥1 TEAE matching the broad search regardless of SSRI/SNRI use in UC (with: 25.4% [n = 17 of 67]; without: 15.0% [n = 164 of 1091]) and RMS (with: 12.4% [n = 34 of 274]; without: 15.6% [n = 310 of 1982]) studies. Conclusions No evidence of increased TEAEs potentially associated with serotonin accumulation was observed with concurrent use of ozanimod and SSRIs/SNRIs. Clinical trial registration NCT01647516, NCT02531126, NCT02435992, NCT02576717 Lay Summary No evidence of increased treatment-emergent adverse effects potentially associated with serotonin accumulation was observed with concurrent use of ozanimod and serotonergic antidepressants. Our findings support the absence of clinically meaningful ozanimod monoamine oxidase B inhibition in vivo. Graphical Abstract Graphical Abstract

• Publisher: Oxford University Press
• Subject: Adult / Antidepressants / Antidepressive Agents - administration & dosage / Clinical Research / Colitis, Ulcerative - drug therapy / Drug Therapy, Combination / Female / Humans / Indans - administration & dosage / Indans - adverse effects / Indans - therapeutic use / Inflammatory bowel disease / Inhibitor drugs / Male / Middle Aged / Multiple sclerosis / Multiple Sclerosis, Relapsing-Remitting - drug therapy / Oxadiazoles - administration & dosage / Oxadiazoles - adverse effects / Oxadiazoles - therapeutic use / Selective Serotonin Reuptake Inhibitors - administration & dosage / Selective Serotonin Reuptake Inhibitors - adverse effects / Selective Serotonin Reuptake Inhibitors - therapeutic use / Serotonin / Sphingosine 1 Phosphate Receptor Modulators - administration & dosage / Sphingosine 1 Phosphate Receptor Modulators - adverse effects