{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:07:05Z","timestamp":1786122425420,"version":"build-2736575974"},"reference-count":20,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Risk &amp; Safety in Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lorlatinib, a third-generation ALK\/ROS1 inhibitor, is highly effective in ALK-positive non\u2013small-cell lung cancer (NSCLC), particularly for intracranial disease. It is associated with a distinctive neuropsychiatric toxicity profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To characterize neuropsychiatric adverse events (AEs) of lorlatinib using FAERS post-marketing data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>FAERS reports listing lorlatinib as the primary suspect (November 2018\u2013December 2024) were analyzed via OpenVigil 2.1. Neuropsychiatric AEs were grouped into four domains: cognitive, mood, speech, and psychotic. Disproportionality was assessed using Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 3452 reports, cognitive effects predominated: cognitive disorder (2.95%, ROR: 16.68, PRR: 16.22), memory impairment (2.35%, ROR: 4.07, PRR: 3.99), and confusional state (1.77%, ROR: 3.22, PRR: 3.18). Mood alterations included affective disorder (0.43%, ROR: 13.13, PRR: 13.08) and personality change (0.32%, ROR: 10.32, PRR: 10.29). Speech disturbances included slow speech (0.2%, ROR: 18.49, PRR: 18.45) and speech disorder (1.22%, ROR: 6.47, PRR: 6.40). Psychiatric manifestations were most pronounced: olfactory hallucinations (0.14%, ROR: 91.44, PRR: 91.31), auditory hallucinations (1.3%, ROR: 22.0, PRR: 21.7), and acute psychosis (0.2%, ROR: 22.12, PRR: 22.07).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lorlatinib exhibits a multidimensional neuropsychiatric profile with rare but highly specific events. Proactive monitoring of cognitive, mood, speech, and psychotic domains is recommended in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09246479261442221","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T22:24:16Z","timestamp":1776119056000},"page":"382-389","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuropsychiatric adverse events associated with lorlatinib in ALK-positive NSCLC"],"prefix":"10.1177","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9092-6588","authenticated-orcid":false,"given":"Eleonora","family":"Castellana","sequence":"first","affiliation":[{"name":"Azienda Ospedaliero Universitaria Citt\u00e0 della Salute e della Scienza di Torino"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rachele","family":"Chiappetta","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero Universitaria Citt\u00e0 della Salute e della Scienza di Torino"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05945"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0318"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30649-1"},{"key":"e_1_3_5_5_2","unstructured":"ClinicalTrials.gov- 2024- A study of lorlatinib versus crizotinib in first line treatment of patients with ALK-positive NSCLC-. https:\/\/www.clinicaltrials.gov\/study\/NCT03052608- last accessed July 2025."},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00581"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02278"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2024.10.018"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0380"},{"key":"e_1_3_5_10_2","unstructured":"FDA Adverse Event Reporting System (FAERS) public dashboard \u2013 2025. https:\/\/www.fda.gov\/drugs\/fdas-adverse-event-reporting-system-faers\/fda-adverse-event-reporting-system-faers-public-dashboard-last accessed July 2025."},{"key":"e_1_3_5_11_2","unstructured":"FDA approves lorlatinib for second- or third-line treatment of ALK-positive metastatic NSCLC. 2018. https:\/\/www.fda.gov\/drugs\/fda-approves-lorlatinib-second-or-third-line-treatment-alk-positive-metastatic-nsclc- last accessed July 2025."},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.orcp.2025.01.011"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/pds.677"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3061"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-024-01379-7"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-01339-9"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2023-0014"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16142611"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare10030420"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/09246479251366836"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.33314\/jnhrc.v19i04.3714"}],"container-title":["International Journal of Risk &amp; 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