Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USA.
Sunovion Pharmaceuticals Inc., Marlborough, Massachusetts, USA.
Epilepsia Open. 2022 Dec;7(4):616-632. doi: 10.1002/epi4.12635. Epub 2022 Aug 30.
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.
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).
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.
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.
依佐加滨醋酸乙酯（ESL）是一种每日一次（QD）的口服抗癫痫药物，用于治疗局灶性（部分发作）癫痫。在这里，我们评估了成人局灶性癫痫患者辅助使用 ESL 临床试验中出现精神科治疗中出现的不良事件（TEAE）的风险因素。
这项事后分析评估了来自三项 III 期、随机、双盲、安慰剂对照试验（BIA-2093-301、-302、-304）的数据汇总。经过 8 周的基线期后，患者被平均随机分为安慰剂组、ESL 400mg 组（此处未报告）、800mg 组或 1200mg QD 组（最多 2 周滴定；12 周维持；可选开放标签扩展[OLE]）。根据三个独立标准评估精神病学 TEAEs 的发生率：精神病史（是/否）；基线期使用精神药物（是/否）；基线期的 Montgomery-Åsberg 抑郁评定量表（MADRS）评分（0-6：正常；7-19：轻度抑郁；20-34：中度抑郁）。
分析人群包括控制研究期间的 1251 例患者和 1 年 OLE 期间的 1137 例患者。在控制和 OLE 研究期间，接受 ESL 和安慰剂治疗的患者之间精神病学 TEAEs 的发生率相似，且与 ESL 剂量无关。精神病学 TEAEs 通常在有精神病史、使用精神药物或有抑郁症状的患者中比没有病史、不使用精神药物或没有抑郁症状的患者更频繁发生。抑郁和焦虑是最常报告的精神病学 TEAEs。
总的来说，在成人局灶性癫痫患者的 ESL 临床试验中，接受 ESL 和安慰剂治疗的患者之间的精神事件发生率没有统计学差异，与 ESL 剂量无关，并且在基线时有精神症状或精神病史的患者中更常见。长期暴露于 ESL 不会导致精神病学 TEAEs 的发生率明显增加。
