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

Inflamm Bowel Dis. 2025 Apr 10;31(4):1010-1017. doi: 10.1093/ibd/izae136.

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.

Keywords: ozanimod; safety; serotonergic antidepressants; serotonin accumulation; ulcerative colitis.

Plain language 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.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidepressive Agents* / administration & dosage
  • Colitis, Ulcerative* / drug therapy
  • Drug Therapy, Combination
  • Female
  • Humans
  • Indans* / administration & dosage
  • Indans* / adverse effects
  • Indans* / therapeutic use
  • Male
  • Middle Aged
  • 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
  • Sphingosine 1 Phosphate Receptor Modulators* / administration & dosage
  • Sphingosine 1 Phosphate Receptor Modulators* / adverse effects

Substances

  • Antidepressive Agents
  • Indans
  • Oxadiazoles
  • ozanimod
  • Selective Serotonin Reuptake Inhibitors
  • Sphingosine 1 Phosphate Receptor Modulators

Associated data

  • ClinicalTrials.gov/NCT01647516
  • ClinicalTrials.gov/NCT02531126
  • ClinicalTrials.gov/NCT02435992
  • ClinicalTrials.gov/NCT02576717

Grants and funding