Department of Child and Adolescent Psychiatry, University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, İstanbul, Turkey.
Department of Pediatric Neurology, University of Health Sciences, Kartal Dr. Lutfi Kirdar City Hospital, Istanbul, Turkey.
Paediatr Drugs. 2024 Nov;26(6):753-765. doi: 10.1007/s40272-024-00652-8. Epub 2024 Sep 27.
Antiseizure medications (ASMs) can potentially trigger psychobehavioral adverse events associated with the onset or exacerbation of psychiatric symptoms such as irritability, aggression, and hyperactivity. The objective of this study was to evaluate the effects of levetiracetam and valproic acid on changes in clinical features of anger, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). The purpose was to furnish guidance on rational drug selection in children and adolescents with epilepsy to minimize psychiatric comorbidity in the treatment of epilepsy.
This was a prospective, observational, cohort study involving treatment-naïve children aged 7-18 years with newly diagnosed generalized or focal epilepsy who were prescribed levetiracetam or valproic acid as monotherapy for a 6-month period and regularly followed up. Psychiatric assessment was conducted at the time of the new epilepsy diagnosis and at the six-month follow-up. These assessments were performed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children Current and Lifetime Version (DSM-5), a structured psychiatric interview, as well as the State-Trait Anger Expression Style Inventory and Turgay DSM-IV Based Disruptive Behaviour Disorders Screening and Rating Scale. Anger subscores, ADHD symptoms, change in diagnosis, focal and generalized epilepsy groups, continuous seizures and seizure-free periods before and 6 months after treatment with valproic acid and levetiracetam were compared.
A total of 50 children, 25 in the valproic acid group and 25 in the levetiracetam group, with a mean age of 11.92 ± 3.08 years, were included in the study. There was a statistically significant increase in the ADHD subscale score post-treatment among patients receiving levetiracetam (p = 0.045) and valproic acid (p = 0.034) compared with pre-treatment. The change in both anger-in and anger-out expression scores with treatment was significantly higher in patients receiving levetiracetam (p = 0.035) compared with those receiving valproic acid (p = 0.026). Statistically, there was a significant difference in the diagnostic criteria of the levetiracetam group pre- and post-treatment (p = 0.026). The proportion of patients in whom the diagnostic criteria for ADHD+ODD were fulfilled increased from 16% before treatment to 48% after treatment, a statistically significant increase (p = 0.026).
This study found an increase in internalized anger features and ADHD symptom severity in children with epilepsy treated with valproic acid and levetiracetam. In those prescribed levetiracetam, there was a statistically significant rise in the proportion meeting the diagnostic criteria for ADHD + ODD. Our research is one of the first to prospectively examine the psychiatric assessment of children diagnosed with epilepsy. The remarkable results demonstrate changes in psychiatric diagnoses associated with the treatment of levetiracetam and valproic acid. Furthermore, a considerable rise in ADHD symptoms was observed in those treated with valproic acid.
抗癫痫药物（ASM）可能会引发与精神病症状相关的精神行为不良事件，如易怒、攻击和多动。本研究的目的是评估左乙拉西坦和丙戊酸对愤怒、注意缺陷多动障碍（ADHD）和对立违抗障碍（ODD）临床特征变化的影响。目的是为癫痫儿童和青少年的合理药物选择提供指导，以最大程度地减少癫痫治疗中的精神共病。
这是一项前瞻性、观察性、队列研究，纳入了 7-18 岁新诊断为全面性或局灶性癫痫且未接受治疗的儿童，他们接受左乙拉西坦或丙戊酸单药治疗，为期 6 个月，并定期随访。在新诊断癫痫时和 6 个月随访时进行精神病评估。这些评估使用了儿童青少年精神障碍诊断与统计手册（DSM-5）的当前和终身版定式访谈、状态特质愤怒表达量表和 Turgay DSM-IV 基于破坏性行为障碍筛查和评分量表。比较了丙戊酸和左乙拉西坦治疗前后的愤怒亚量表评分、ADHD 症状、诊断变化、局灶性和全面性癫痫组、连续发作和治疗前和治疗后 6 个月无发作期。
共有 50 名儿童（丙戊酸组 25 名，左乙拉西坦组 25 名），平均年龄为 11.92±3.08 岁，纳入本研究。与治疗前相比，接受左乙拉西坦（p=0.045）和丙戊酸（p=0.034）治疗后 ADHD 亚量表评分显著升高。与接受丙戊酸治疗的患者相比，接受左乙拉西坦治疗的患者愤怒表达和愤怒抑制得分的变化与治疗相关，差异具有统计学意义（p=0.035）。与接受丙戊酸治疗的患者相比，接受左乙拉西坦治疗的患者在治疗前后的诊断标准（p=0.026）显著不同。治疗前后，ADHD+ODD 诊断标准满足的患者比例从治疗前的 16%增加到治疗后的 48%，差异有统计学意义（p=0.026）。
本研究发现，丙戊酸和左乙拉西坦治疗的癫痫儿童愤怒内化特征和 ADHD 症状严重程度增加。接受左乙拉西坦治疗的患者中，符合 ADHD+ODD 诊断标准的比例有统计学意义的增加（p=0.026）。我们的研究是第一个前瞻性检查癫痫儿童精神病评估的研究之一。这一显著结果表明，丙戊酸和左乙拉西坦治疗与精神病诊断的变化有关。此外，接受丙戊酸治疗的患者 ADHD 症状明显增加。
