{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:36:36Z","timestamp":1790933796579,"version":"4.1.0"},"reference-count":19,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n In March 2020, the US Food and Drug Administration (FDA) issued a boxed warning for montelukast amid reports of neuropsychiatric adverse effects.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine whether a boxed warning for montelukast was associated with changes in prescription rates of montelukast to treat asthma in the US.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n In this serial cross-sectional study using a national commercial insurance claims database, monthly cohorts of individuals aged 6 years and older with an asthma diagnosis and continuous insurance coverage in the past year were created from October 2017 to December 2022. Results were stratified by age group, inhaled corticosteroid (ICS) use, and 1 or more asthma-related emergency department visit or hospitalization in the prior year. Data were analyzed from August 2024 to June 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Announcement of a boxed warning for montelukast in March 2020.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Monthly incidence and prevalence of montelukast use among patients with asthma. Data were analyzed with an interrupted time series analysis using segmented ordinary least-squares linear regression models with Newey-West standard errors.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The number of patients with asthma ranged from 594\u202f253 in October 2017 to 614\u202f637 in December 2022. In October 2017, 348\u202f359 patients (58.6%) were female, 113\u202f913 (19.2%) were younger than age of 18 years, 292\u202f730 (49.3%) used an ICS, and 105\u202f869 (17.8%) had 1 or more asthma-related emergency department visit or hospitalization in the prior year. The baseline monthly prevalence of montelukast use was 160.0 per 1000 patients with asthma, and the baseline incidence of new montelukast use was 5.8 per 1000. After the boxed warning, the level of monthly incident montelukast prescriptions decreased by 1.7 (95% CI, \u22122.2 to \u22121.3) per 1000 and the trend in montelukast prevalence decreased by 0.9 (95% CI, \u22121.1 to \u22120.6) per 1000 per month relative to the prewarning trend. The trend in prevalent montelukast use decreased after the boxed warning across all age and asthma severity subgroups.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and relevance<\/jats:title>\n In this cross-sectional study of commercially insured patients with asthma, an FDA boxed warning for montelukast was associated with changes in asthma treatment use among patients of all ages.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.14274","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T15:30:21Z","timestamp":1779463821000},"page":"e2614274","source":"Crossref","is-referenced-by-count":4,"title":["Changes in the Use of Montelukast for Asthma After a US Food and Drug Administration Boxed Warning"],"prefix":"10.1001","volume":"9","author":[{"given":"Hariharan","family":"Shanmugam","sequence":"first","affiliation":[{"name":"Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron S.","family":"Kesselheim","sequence":"additional","affiliation":[{"name":"Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian T. T.","family":"Liu","sequence":"additional","affiliation":[{"name":"Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Feldman","sequence":"additional","affiliation":[{"name":"Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"},{"name":"Division of Pulmonary, Critical Care, Sleep Medicine, Clinical Immunology, and Allergy, Department of Medicine, University of California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin N.","family":"Rome","sequence":"additional","affiliation":[{"name":"Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"issue":"169","key":"zoi260418r1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0079-2023","article-title":"Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review.","volume":"32","author":"Lo","year":"2023","journal-title":"Eur Respir Rev"},{"issue":"7","key":"zoi260418r2","doi-asserted-by":"publisher","first-page":"2638","DOI":"10.1016\/j.jaip.2021.02.057","article-title":"A boxed warning for montelukast: the FDA perspective.","volume":"9","author":"Clarridge","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"1","key":"zoi260418r3","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.jaip.2020.07.052","article-title":"Risk of psychiatric adverse events among montelukast users.","volume":"9","author":"Sansing-Foster","year":"2021","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"4","key":"zoi260418r4","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1001\/jamapediatrics.2024.5429","article-title":"Montelukast use and the risk of neuropsychiatric adverse events in children.","volume":"179","author":"Wintzell","year":"2025","journal-title":"JAMA Pediatr"},{"issue":"2","key":"zoi260418r5","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00148-2017","article-title":"Neuropsychiatric adverse drug reactions in children initiated on montelukast in real-life practice.","volume":"50","author":"Benard","year":"2017","journal-title":"Eur Respir J"},{"key":"zoi260418r6","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.jpeds.2019.02.009","article-title":"Montelukast and neuropsychiatric events in children with asthma: a nested case-control study.","volume":"209","author":"Glockler-Lauf","year":"2019","journal-title":"J Pediatr"},{"issue":"1","key":"zoi260418r7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s40264-015-0360-2","article-title":"Psychiatric disorders and montelukast in children: a disproportionality analysis of the VigiBase.","volume":"39","author":"Aldea Perona","year":"2016","journal-title":"Drug Saf"},{"issue":"9","key":"zoi260418r9","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1176\/appi.ajp.2007.07030454","article-title":"Early evidence on the effects of regulators\u2019 suicidality warnings on SSRI prescriptions and suicide in children and adolescents.","volume":"164","author":"Gibbons","year":"2007","journal-title":"Am J Psychiatry"},{"issue":"6","key":"zoi260418r10","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1038\/ajg.2012.300","article-title":"The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits.","volume":"108","author":"Ehrenpreis","year":"2013","journal-title":"Am J Gastroenterol"},{"key":"zoi260418r11","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.drugalcdep.2017.03.021","article-title":"Trends in utilization of smoking cessation agents before and after the passage of FDA boxed warning in the United States.","volume":"177","author":"Shah","year":"2017","journal-title":"Drug Alcohol Depend"},{"key":"zoi260418r12","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jss.2020.06.023","article-title":"Continued prescribing of periprocedural codeine and tramadol to children after a black box warning.","volume":"256","author":"Kohler","year":"2020","journal-title":"J Surg Res"},{"issue":"12","key":"zoi260418r13","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.36662","article-title":"Association of fluoroquinolone prescribing rates with black box warnings from the US Food and Drug Administration.","volume":"4","author":"Sankar","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"3","key":"zoi260418r14","doi-asserted-by":"publisher","DOI":"10.1136\/bmjoq-2024-002925","article-title":"Impact of the US Food and Drug Administration warning regarding increased risk of aortic aneurysms or aortic dissections on fluoroquinolone prescribing trends.","volume":"13","author":"Rizk","year":"2024","journal-title":"BMJ Open Qual"},{"issue":"6S","key":"zoi260418r15","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.12788\/jfp.0219","article-title":"National asthma education and prevention program 2020 guidelines: What\u2019s important for primary care.","volume":"70","author":"Murphy","year":"2021","journal-title":"J Fam Pract"},{"issue":"6","key":"zoi260418r16","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1097\/MLR.0b013e318245a160","article-title":"Impact of FDA drug risk communications on health care utilization and health behaviors: a systematic review.","volume":"50","author":"Dusetzina","year":"2012","journal-title":"Med Care"},{"issue":"2","key":"zoi260418r18","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.jaip.2019.08.024","article-title":"Trends and disparities in asthma biologic use in the United States.","volume":"8","author":"Inselman","year":"2020","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"4","key":"zoi260418r19","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1080\/02770903.2021.1881967","article-title":"Montelukast in hospitalized patients diagnosed with COVID-19.","volume":"59","author":"Khan","year":"2022","journal-title":"J Asthma"},{"key":"zoi260418r8","unstructured":"Singulair (montelukast sodium) tablets, chewable tablets, and oral granules: highlights of prescribing information. US Food and Drug Administration. Accessed February 23, 2026. https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=overview.process&ApplNo=020829"},{"key":"zoi260418r17","unstructured":"Jewett? C, Mueller? B. The FDA warned an asthma drug could induce despair. many were never told. New York Times. Accessed March 12, 2025. https:\/\/www.nytimes.com\/2024\/01\/09\/health\/fda-singulair-asthma-drug-warning.html"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2849283\/shanmugam_2026_oi_260418_1778857506.82442.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T15:30:24Z","timestamp":1779463824000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2849283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.14274","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]}}}