{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T06:21:32Z","timestamp":1783405292050,"version":"3.54.6"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atorvastatin, a widely prescribed HMG-CoA reductase inhibitor, is associated with neurological adverse events (NAEs) beyond its well-known myopathy; however, comprehensive evaluations accounting for confounding by indication remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A disproportionality analysis was performed using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004\u2013Q3 2025) with three signal detection algorithms (PRR, BCPNN, and MGPS). Signal criteria were: PRR\u202f\u2265\u202f2, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f\u2265\u202f4, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f&amp;gt;\u202f2, IC\n                      <jats:sub>025<\/jats:sub>\n                      \u202f&amp;gt;\u202f0. To minimize confounding by indication, reports with indications for hypercholesterolemia or coronary artery disease (i.e., the approved label indications of atorvastatin) were excluded.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 50 NAE signals identified for atorvastatin, 32 remained significant after exclusion. The strongest signals clustered into three clinically meaningful categories: neuromuscular junction disorders (myasthenia gravis: PRR\u202f=\u202f5.65, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f748.22, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f4.82), peripheral neuropathies (axonal neuropathy: PRR\u202f=\u202f6.15, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f117.78, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f4.14; peripheral sensory neuropathy: PRR\u202f=\u202f3.42, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f182.34, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f2.80), and central nervous system and cognitive disorders (encephalitis toxic: PRR\u202f=\u202f7.76, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f17.11, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f2.39; brain fog: PRR\u202f=\u202f2.94, \u03c7\n                      <jats:sup>2<\/jats:sup>\n                      \u202f=\u202f168.76, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f2.46). Additionally, exceptionally strong signals without detailed published case support included acute necrotising myelitis (PRR\u202f=\u202f832.92, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f38.61), vibration syndrome (PRR\u202f=\u202f37.02, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f14.51), and radiculitis brachial (PRR\u202f=\u202f26.03, EBGM\n                      <jats:sub>05<\/jats:sub>\n                      \u202f=\u202f13.57).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified multiple strong neurological safety signals associated with atorvastatin using a rigorous disproportionality analysis with adjustment for confounding by indication. These findings provide valuable real-world evidence to guide clinical monitoring and warrant further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1852942","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:48:35Z","timestamp":1783403315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Atorvastatin-associated neurological adverse events: a disproportionality analysis with adjustment for confounding by indication"],"prefix":"10.3389","volume":"13","author":[{"given":"Xinjun","family":"He","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Hangzhou Third People\u2019s Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hangzhou Third People\u2019s Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hangzhou Third People\u2019s Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hangzhou Third People\u2019s Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinchang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hangzhou Third People\u2019s Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1001\/jama.2023.2487","article-title":"Treat-to-target or high-intensity statin in patients with coronary 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