Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures
Abstract Objective Eslicarbazepine acetate (ESL) is a once‐daily (QD), oral anti‐seizure medication for the treatment of focal (partial‐onset) seizures. Here, we evaluate risk factors for the development of psychiatric treatment‐emergent adverse events (TEAEs) in clinical trials of adjunctive ESL in...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Epilepsia Open |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/epi4.12635 |
| _version_ | 1797988036576804864 |
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| author | Hamada Altalib Todd Grinnell David Cantu Fábio Ikedo Mariana Vieira Yi Zhang David Blum |
| author_facet | Hamada Altalib Todd Grinnell David Cantu Fábio Ikedo Mariana Vieira Yi Zhang David Blum |
| author_sort | Hamada Altalib |
| collection | DOAJ |
| description | Abstract Objective Eslicarbazepine acetate (ESL) is a once‐daily (QD), oral anti‐seizure medication for the treatment of focal (partial‐onset) seizures. Here, we evaluate risk factors for the development of psychiatric treatment‐emergent adverse events (TEAEs) in clinical trials of adjunctive ESL in adults with focal seizures. Methods This post‐hoc analysis evaluated data pooled from three Phase III, randomized, double‐blind, placebo‐controlled trials (BIA‐2093‐301, ‐302, ‐304). After an 8‐week baseline period, patients were randomized equally to receive placebo, ESL 400 mg (not reported here), 800 mg, or 1200 mg QD (up to 2‐week titration; 12‐week maintenance; optional open‐label extension [OLE]). Incidences of psychiatric TEAEs were evaluated according to three separate criteria: medical history of psychiatric disorders (yes/no); baseline use of psychotropic drugs (yes/no); Montgomery–Åsberg Depression Rating Scale (MADRS) score at baseline (0–6: normal; 7–19: mild depression; 20–34: moderate depression). Results The analysis populations comprised 1251 patients for the controlled study period and 1137 patients for the 1‐year OLE. Psychiatric TEAE incidence was similar between patients taking ESL and placebo in the controlled and OLE study periods and was not related to ESL dose. Psychiatric TEAEs generally occurred more frequently in patients with a medical history of psychiatric disorders, using psychotropic drugs, or with depressive symptoms than in those without a history, not using psychotropic drugs, or with no depressive symptoms. Depression and anxiety were the most frequently reported psychiatric TEAEs. Significance Overall, in clinical trials of ESL in adults with focal seizures, incidences of psychiatric events were not statistically different between patients taking ESL and placebo, were not related to ESL dose, and generally occurred more frequently in patients with baseline psychiatric symptoms or a history of psychiatric disorders. Long‐term exposure to ESL was not associated with a marked increase in the incidence of psychiatric TEAEs. |
| first_indexed | 2024-04-11T07:56:19Z |
| format | Article |
| id | doaj.art-d3026b02cce5409bb9490b2ea2f5cf9d |
| institution | Directory Open Access Journal |
| issn | 2470-9239 |
| language | English |
| last_indexed | 2024-04-11T07:56:19Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Epilepsia Open |
| spelling | doaj.art-d3026b02cce5409bb9490b2ea2f5cf9d2022-12-22T04:35:55ZengWileyEpilepsia Open2470-92392022-12-017461663210.1002/epi4.12635Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizuresHamada Altalib0Todd Grinnell1David Cantu2Fábio Ikedo3Mariana Vieira4Yi Zhang5David Blum6Department of Neurology Yale School of Medicine New Haven Connecticut USASunovion Pharmaceuticals Inc. Marlborough Massachusetts USASunovion Pharmaceuticals Inc. Fort Lee New Jersey USAPharmacovigilance Compliance BIAL – Portela & Cª, S.A. São Mamede do Coronado PortugalPharmacovigilance Compliance BIAL – Portela & Cª, S.A. São Mamede do Coronado PortugalSunovion Pharmaceuticals Inc. Marlborough Massachusetts USASunovion Pharmaceuticals Inc. Marlborough Massachusetts USAAbstract Objective Eslicarbazepine acetate (ESL) is a once‐daily (QD), oral anti‐seizure medication for the treatment of focal (partial‐onset) seizures. Here, we evaluate risk factors for the development of psychiatric treatment‐emergent adverse events (TEAEs) in clinical trials of adjunctive ESL in adults with focal seizures. Methods This post‐hoc analysis evaluated data pooled from three Phase III, randomized, double‐blind, placebo‐controlled trials (BIA‐2093‐301, ‐302, ‐304). After an 8‐week baseline period, patients were randomized equally to receive placebo, ESL 400 mg (not reported here), 800 mg, or 1200 mg QD (up to 2‐week titration; 12‐week maintenance; optional open‐label extension [OLE]). Incidences of psychiatric TEAEs were evaluated according to three separate criteria: medical history of psychiatric disorders (yes/no); baseline use of psychotropic drugs (yes/no); Montgomery–Åsberg Depression Rating Scale (MADRS) score at baseline (0–6: normal; 7–19: mild depression; 20–34: moderate depression). Results The analysis populations comprised 1251 patients for the controlled study period and 1137 patients for the 1‐year OLE. Psychiatric TEAE incidence was similar between patients taking ESL and placebo in the controlled and OLE study periods and was not related to ESL dose. Psychiatric TEAEs generally occurred more frequently in patients with a medical history of psychiatric disorders, using psychotropic drugs, or with depressive symptoms than in those without a history, not using psychotropic drugs, or with no depressive symptoms. Depression and anxiety were the most frequently reported psychiatric TEAEs. Significance Overall, in clinical trials of ESL in adults with focal seizures, incidences of psychiatric events were not statistically different between patients taking ESL and placebo, were not related to ESL dose, and generally occurred more frequently in patients with baseline psychiatric symptoms or a history of psychiatric disorders. Long‐term exposure to ESL was not associated with a marked increase in the incidence of psychiatric TEAEs.https://doi.org/10.1002/epi4.12635anxietydepressioneslicarbazepine acetatefocal seizurespsychiatricpsychotropic |
| spellingShingle | Hamada Altalib Todd Grinnell David Cantu Fábio Ikedo Mariana Vieira Yi Zhang David Blum Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures Epilepsia Open anxiety depression eslicarbazepine acetate focal seizures psychiatric psychotropic |
| title | Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures |
| title_full | Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures |
| title_fullStr | Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures |
| title_full_unstemmed | Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures |
| title_short | Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures |
| title_sort | psychiatric adverse events in three phase iii trials of eslicarbazepine acetate for focal seizures |
| topic | anxiety depression eslicarbazepine acetate focal seizures psychiatric psychotropic |
| url | https://doi.org/10.1002/epi4.12635 |
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