{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:07:25Z","timestamp":1788858445268,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"am","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>CFTR modulators (CFTRms) have transformed cystic fibrosis care, yet concern exists regarding their mental health safety profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To provide further information, we conducted an analysis of CFTRm-related mental health disorders using two spontaneous pharmacovigilance reporting databases in real-world settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed reports from the French Pharmacovigilance Database (FPD) and VigiBase, the WHO global individual case safety reports database. Reports recorded between 2012 and 2024 involving any CFTRm and psychiatric disorders were included. In VigiBase, we conducted a case-non case, disproportionality analysis using the Reporting Odds Ratio (ROR), overall and stratified by age group (pediatrics vs. adults) and by CFTRm type. This study was conducted in accordance with the STROBE and the READUS-PV guidelines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the FPD, 116 cases were analyzed. ELX\/TEZ\/IVA was suspected in 98% of cases and no single case was reported with ivacaftor alone. Sleep (61%), mood (37%), and anxiety disorders (27%) were the most frequently reported, with suicidal behaviors being infrequent, including 6 suicide attempts and no completed suicide. In VigiBase (n\u2009=\u20093,407), sleep disorders predominated in children, whereas mood and suicidality disorders were most frequent in adolescents. The median time to onset was 60 days (Q1-Q3: 12\u2014150 days). Mental health disorders were disproportionately reported with CFTRms, particularly ELX\/TEZ\/IVA, while they were not with other combination therapies, compared to other drugs in the database. Disproportionality signals were slightly stronger in pediatrics than in adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CFTRms, especially ELX\/TEZ\/IVA, are associated with increased reporting of mental health disorders, predominantly sleep and mood disorders. Pediatrics appear to be particularly affected. Prospective observational studies are warranted to confirm these findings and elucidate underlying pathophysiological mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>OSF: mfyx3<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/annalsats\/aaoag192","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:12:37Z","timestamp":1788855157000},"source":"Crossref","is-referenced-by-count":0,"title":["Mental health safety profile of CFTR modulators in pediatrics and adults: insights from the French pharmacovigilance database and from VigiBase"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7669-2339","authenticated-orcid":false,"given":"Diane A","family":"Merino","sequence":"first","affiliation":[{"name":"University Department of Child and Adolescent Psychiatry, Children's Hospitals of Nice, CHU-Lenval , Nice, France"},{"name":"University Hospital of Nice Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5462-0625","authenticated-orcid":false,"given":"Samuel D","family":"Cohen","sequence":"additional","affiliation":[{"name":"Regional Center of Pharmacovigilance , Department of perinatal, pediatric and adult pharmacology, . Paris,","place":["France"]},{"name":"Hopital Cochin, Hopital Necker, Assistance Publique \u2013 Hopitaux de Paris , Department of perinatal, pediatric and adult pharmacology, . Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-5020","authenticated-orcid":false,"given":"Nouha","family":"Ben Othman","sequence":"additional","affiliation":[{"name":"University Hospital of Nice Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7472-8780","authenticated-orcid":false,"given":"Marie-No\u00eblle","family":"Osmont","sequence":"additional","affiliation":[{"name":"Rennes University Hospital Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Department of Clinical Pharmacology, , 35033, Rennes,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6466-7776","authenticated-orcid":false,"given":"Tessa","family":"Pietri","sequence":"additional","affiliation":[{"name":"Centre r\u00e9gional de pharmacovigilance Marseille Provence Corse Service de pharmacologie Clinique & Pharmacosurveillance, , , Marseille, France"},{"name":"AMU INSERM 1106 Institut de Neurosciences des Syst\u00e8mes, Assistance Publique \u2013 H\u00f4pitaux de Marseille Service de pharmacologie Clinique & Pharmacosurveillance, , , Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Bergeron","sequence":"additional","affiliation":[{"name":", U 1171 University Hospital of Lille, University of Lille Regional Pharmacovigilance Centre Lille, Clinical Pharmacology Department , F-59000 Lille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6557-8757","authenticated-orcid":false,"given":"Sophie","family":"Gautier","sequence":"additional","affiliation":[{"name":", U 1171 University Hospital of Lille, University of Lille Regional Pharmacovigilance Centre Lille, Clinical Pharmacology Department , F-59000 Lille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5835-6224","authenticated-orcid":false,"given":"Fanny","family":"Rocher","sequence":"additional","affiliation":[{"name":"University Hospital of Nice Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4121-530X","authenticated-orcid":false,"given":"Milou-Daniel","family":"Drici","sequence":"additional","affiliation":[{"name":"University Hospital of Nice Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0903-9828","authenticated-orcid":false,"given":"Pierre-R\u00e9gis","family":"Burgel","sequence":"additional","affiliation":[{"name":"H\u00f4pital Cochin and Cystic Fibrosis National Reference Center, Service de Pneumologie, Assistance Publique-H\u00f4pitaux de Paris , Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5537-9482","authenticated-orcid":false,"given":"Isabelle","family":"Sermet-Gaudelus","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Mucoviscidose et Maladies Apparent\u00e9es , , , , Institut Necker Enfants Malades, INSERM U1151, Paris 75015,","place":["France"]},{"name":"H\u00f4pital Necker Enfants malades , , , , Institut Necker Enfants Malades, INSERM U1151, Paris 75015,","place":["France"]},{"name":"Assistance Publique H\u00f4pitaux de Paris , , , , Institut Necker Enfants Malades, INSERM U1151, Paris 75015,","place":["France"]},{"name":"Groupe Hospitalier Paris Centre , , , , Institut Necker Enfants Malades, INSERM U1151, Paris 75015,","place":["France"]},{"name":"ERN Lung , Frankfurt,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6591-6966","authenticated-orcid":false,"given":"Alexandre O","family":"G\u00e9rard","sequence":"additional","affiliation":[{"name":"University Hospital of Nice Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]},{"name":"Universit\u00e9 C\u00f4te d\u2019Azur Department of Clinical Pharmacology and Pharmacovigilance Center of Nice, , , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-3571","authenticated-orcid":false,"given":"Laurent","family":"Chouchana","sequence":"additional","affiliation":[{"name":"Regional Center of Pharmacovigilance , Department of perinatal, pediatric and adult pharmacology, . Paris,","place":["France"]},{"name":"Hopital Cochin, Hopital Necker, Assistance Publique \u2013 Hopitaux de Paris , Department of perinatal, pediatric and adult pharmacology, . Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,7]]},"container-title":["Annals of the American Thoracic Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/annalsats\/advance-article-pdf\/doi\/10.1093\/annalsats\/aaoag192\/70989169\/aaoag192.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/annalsats\/advance-article-pdf\/doi\/10.1093\/annalsats\/aaoag192\/70989169\/aaoag192.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:12:37Z","timestamp":1788855157000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/annalsats\/advance-article\/doi\/10.1093\/annalsats\/aaoag192\/8787740"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/annalsats\/aaoag192","relation":{},"ISSN":["2325-6621"],"issn-type":[{"value":"2325-6621","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"aaoag192"}}