BACKGROUND: Monoamine oxidase (MAO) inhibitors can interact with selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs). There is clinical interest surrounding use of ozanimod with SSRIs/SNRIs because the major metabolites of ozanimod are weak inhibitors of MAO-B in vitro. OBJECTIVE: To evaluate the incidence of treatment-emergent adverse events (TEAEs) potentially related to serotonin accumulation (SA) during concomitant ozanimod and SSRI/SNRI use by performing analyses of data from an open-label, oral ozanimod 0.92 mg trial (DAYBREAK; NCT02576717). METHODS: SA narrow (serotonin syndrome, neuroleptic malignant syndrome, and hyperthermia malignant) and broad (terms potentially associated with SA) MedDRA v24.0 searches were performed using TEAE data from participants with relapsing multiple sclerosis who entered DAYBREAK from phase 3 studies (cutoff February 1, 2022). Incidences of TEAEs matching terms from each search were stratified by SSRI/SNRI use. RESULTS: Of 2257 DAYBREAK participants, 274 (12.1%) used an SSRI/SNRI. No participants had TEAEs matching the SA narrow search terms. There was no significant difference in the percentage of participants with ⩾1 TEAE matching the SA broad search for those on versus off SSRIs/SNRIs (on: 12.4%, n = 34/274; off: 15.6%, n = 310/1982, nominal p = 0.1630). CONCLUSION: MedDRA searches showed no increase in TEAEs potentially associated with SA with concomitant SSRI/SNRI and ozanimod use.

Brain and Mind Centre The University of Sydney Sydney NSW Australia

Bristol Myers Squibb Princeton NJ USA

Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia PA USA

Center for Neurology Łódź Poland

Collegium Medicum Department of Neurology University of Warmia and Mazury in Olsztyn Olsztyn Poland

Department of Neurology Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany

Department of Neurology Medical University of Vienna Vienna Austria

Mellen Center for MS Treatment and Research Cleveland Clinic Cleveland OH USA

Palacký University Olomouc Olomouc Czech Republic

Vita Salute San Raffaele University and Casa di Cura Igea Milan Italy

Washington University School of Medicine St Louis MO USA

Weill Institute for Neurosciences Department of Neurology University of California San Francisco San Francisco CA USA

Zobrazit více v PubMed

Boeschoten RE, Braamse AMJ, Beekman ATF, et al.. Prevalence of depression and anxiety in multiple sclerosis: A systematic review and meta-analysis. J Neurol Sci 2017; 372: 331–341. PubMed

Garakani A, Murrough JW, Freire RC, et al.. Pharmacotherapy of anxiety disorders: Current and emerging treatment options. Front Psychiatry 2020; 11: 595584. PubMed PMC

Ghaffari Darab M, Hedayati A, Khorasani E, et al.. Selective serotonin reuptake inhibitors in major depression disorder treatment: An umbrella review on systematic reviews. Int J Psychiatry Clin Pract 2020; 24(4): 357–370. PubMed

Chu A, Wadhwa R. Selective serotonin reuptake inhibitors. Treasure Island, FL: StatPearls Publishing, 2022. PubMed

Gelenberg AJ, Freeman MP, Markowitz JC, et al.. Practice guideline for the treatment of patients with major depressive disorder. Washington, DC: American Psychiatric Association.2010.

Foong AL, Grindrod KA, Patel T, et al.. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Physician 2018; 64(10): 720–727. PubMed PMC

Zeposia (package insert). Princeton, NJ: Bristol Myers Squibb, 2023.

Zeposia (summary of product characteristics). Utrecht: Celgene Distribution B.V., 2023.

Surapaneni S, Yerramilli U, Bai A, et al.. Absorption, metabolism, and excretion, in vitro pharmacology, and clinical pharmacokinetics of ozanimod, a novel sphingosine 1-phosphate receptor agonist. Drug Metab Dispos 2021; 49: 405–419. PubMed

Tran JQ, Zhang P, Walker S, et al.. Multiple-dose pharmacokinetics of ozanimod and its major active metabolites and the pharmacodynamic and pharmacokinetic interactions with pseudoephedrine, a sympathomimetic agent, in healthy subjects. Adv Ther 2020; 37(12): 4944–4958. PubMed PMC

Cohen JA, Comi G, Selmaj KW, et al.. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): A multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol 2019; 18(11): 1021–1033. PubMed

Comi G, Kappos L, Selmaj KW, et al.. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): A multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol 2019; 18(11): 1009–1020. PubMed

Cree BA, Selmaj KW, Steinman L, et al.. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: Up to 5 years of follow-up in the DAYBREAK open-label extension trial. Mult Scler 2022; 28: 1944–1962. PubMed PMC

Common questions about trazodone . London: National Health Services, 2022.

Prakash S, Rathore C, Rana KK, et al.. Refining the clinical features of serotonin syndrome: A prospective observational study of 45 patients. Ann Indian Acad Neurol 2019; 22(1): 52–60. PubMed PMC

Cantalupo A, Gargiulo A, Dautaj E, et al.. S1PR1 (sphingosine-1-phosphate receptor 1) signaling regulates blood flow and pressure. Hypertension 2017; 70(2): 426–434. PubMed PMC

Tse L, Barr AM, Scarapicchia V, et al.. Neuroleptic malignant syndrome: A review from a clinically oriented perspective. Curr Neuropharmacol 2015; 13(3): 395–406. PubMed PMC

Lexapro (package insert). Irvine, CA: Allergan, 2017.

Richard IH, Kurlan R, Tanner C, et al.. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Parkinson study group. Neurology 1997; 48(4): 1070–1077. PubMed

Hilli J, Korhonen T, Laine K. Lack of clinically significant interactions between concomitantly administered rasagiline and escitalopram. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 1526–1532. PubMed

Laine K, Anttila M, Heinonen E, et al.. Lack of adverse interactions between concomitantly administered selegiline and citalopram. Clin Neuropharmacol 1997; 20(5): 419–433. PubMed

Panisset M, Chen JJ, Rhyee SH, et al.. Serotonin toxicity association with concomitant antidepressants and rasagiline treatment: Retrospective study (STACCATO). Pharmacotherapy 2014; 34(12): 1250–1258. PubMed

Aboukarr A, Giudice M. Interaction between monoamine oxidase B inhibitors and selective serotonin reuptake inhibitors. Can J Hosp Pharm 2018; 71(3): 196–207. PubMed PMC

Williams RB, Marchuk DA, Gadde KM, et al.. Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology 2003; 28(3): 533–541. PubMed

Zobrazit více v PubMed

ClinicalTrials.gov
NCT02576717