{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:52:28Z","timestamp":1790502748799,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T00:00:00Z","timestamp":1435881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Eisai Inc."},{"name":"Imprint Publication Science, New York, NY"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Perampanel, a selective, noncompetitive \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid (AMPA) glutamate receptor antagonist, is indicated for adjunctive treatment of partial seizures in patients \u226512\u00a0years based on three phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> clinical studies. The perampanel <jats:styled-content style=\"fixed-case\">U.S.<\/jats:styled-content> Prescribing Information includes a boxed warning for serious psychiatric and behavioral adverse reactions. To provide context for this warning, detail on psychiatric and behavioral safety data from perampanel clinical studies is presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An analysis of pooled safety data from three phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> studies in patients with partial seizures is presented. Data from phase I and phase <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> studies in patients with and without epilepsy were also analyzed. Psychiatric and behavioral treatment\u2010emergent adverse events (<jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s) were evaluated according to Medical Dictionary for Regulatory Activities (Med<jats:styled-content style=\"fixed-case\">DRA<\/jats:styled-content>) terms, using \u201cnarrow\u201d and \u201cnarrow\u2010and\u2010broad\u201d standardized Med<jats:styled-content style=\"fixed-case\">DRA<\/jats:styled-content> queries (<jats:styled-content style=\"fixed-case\">SMQ<\/jats:styled-content>s) for <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s suggestive of hostility\/aggression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From the three phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> partial\u2010seizure studies, the overall rate of psychiatric <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s was higher in the 8\u00a0mg (17.2%) and 12\u00a0mg (22.4%) perampanel groups versus placebo (12.4%). In the \u201cnarrow\u201d <jats:styled-content style=\"fixed-case\">SMQ<\/jats:styled-content>, hostility\/aggression <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s were observed in 2.8% for 8\u00a0mg and 6.3% for 12\u00a0mg perampanel groups, versus 0.7% of placebo patients. \u201cNarrow\u2010and\u2010broad\u201d <jats:styled-content style=\"fixed-case\">SMQ<\/jats:styled-content>s for hostility\/aggression <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content> rates were 12.3% for 8\u00a0mg and 20.4% for 12\u00a0mg perampanel groups, versus 5.7% for placebo; rates for events resulting in discontinuation were perampanel\u00a0=\u00a01.6% versus placebo\u00a0=\u00a00.7%. For events reported as serious <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s (<jats:styled-content style=\"fixed-case\">SAE<\/jats:styled-content>s), rates were perampanel\u00a0=\u00a00.7% versus placebo\u00a0=\u00a00.2%. In nonepilepsy patients, psychiatric <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s were similar between patients receiving perampanel and placebo. In phase I subjects\/volunteers, all psychiatric <jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s were mild or moderate. These analyses suggest that psychiatric adverse effects are associated with use of perampanel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Patients and caregivers should be counseled regarding the potential risk of psychiatric and behavioral events with perampanel in patients with partial seizures; patients should be monitored for these events during treatment, especially during titration and at higher doses.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13054","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T18:14:01Z","timestamp":1435947241000},"page":"1252-1263","source":"Crossref","is-referenced-by-count":135,"title":["Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive <scp>AMPA<\/scp> receptor antagonist perampanel"],"prefix":"10.1111","volume":"56","author":[{"given":"Alan B.","family":"Ettinger","sequence":"first","affiliation":[{"name":"Department of Clinical Neurology Albert Einstein College of Medicine Bronx New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"LoPresti","sequence":"additional","affiliation":[{"name":"Eisai Medical and Scientific Affairs Eisai Inc. Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichen","family":"Yang","sequence":"additional","affiliation":[{"name":"Eisai Neuroscience and General Medicine PCU Eisai Inc. Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy","family":"Williams","sequence":"additional","affiliation":[{"name":"Eisai Medical and Scientific Affairs Eisai Inc. Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Zhou","sequence":"additional","affiliation":[{"name":"Eisai Medical and Scientific Affairs Eisai Inc. Woodcliff Lake New Jersey U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi","family":"Fain","sequence":"additional","affiliation":[{"name":"Eisai Medical and Scientific Affairs Eisai Inc. 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