Chen Ziyi, Lusicic Ana, O'Brien Terence J, Velakoulis Dennis, Adams Sophia J, Kwan Patrick
1 Departments of Medicine and Neurology, The Melbourne Brain Centre, The University of Melbourne, The Royal Melbourne Hospital, Victoria, Australia 2 Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
3 Melbourne Neuropsychiatry Centre, The University of Melbourne, The Royal Melbourne Hospital, Victoria, Australia.
Brain. 2016 Oct;139(Pt 10):2668-2678. doi: 10.1093/brain/aww196. Epub 2016 Aug 8.
Antiepileptic drug treatment can induce psychosis in some patients. However, there are no agreed definitions or diagnostic criteria for antiepileptic drug-induced psychotic disorder in the classification systems of either epileptology or psychiatry. In this study we investigated the clinical spectrum of antiepileptic drug-induced psychotic disorder in patients with epilepsy. The medical records of all patients with epilepsy who were diagnosed by a neuropsychiatrist as having a psychotic disorder at the Royal Melbourne Hospital from January 1993 to June 2015 were reviewed. Data were extracted regarding epilepsy and its treatment, psychotic symptoms profile and outcome. The diagnosis of epilepsy was established in accordance to the classification system of the International League Against Epilepsy while that of psychotic disorder was made according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition and the proposal on neuropsychiatric disorders in epilepsy. Patients with antiepileptic drug-induced psychotic disorder were compared to those with psychotic disorders unrelated to antiepileptic drugs assessed over the same period (non-antiepileptic drug induced psychotic disorder group). Univariate comparisons were performed and variables with a value of P < 0.1 were selected for the multivariate logistic regression analysis. The records of 2630 in-patients and outpatients with epilepsy were screened, from which 98 (3.7%) with psychotic disorders were identified. Among these, 14 (14.3%) were diagnosed to have antiepileptic drug-induced psychotic disorder. Excluding one patient who developed psychosis after valproate withdrawal, 76.9% in the antiepileptic drug induced psychotic disorder group were female and the percentage of temporal lobe involvement was higher in the antiepileptic drug induced psychotic disorder group (69.2% versus 38.1%, P < 0.05). Current use of levetiracetam was higher in antiepileptic drug-induced psychotic disorder group (84.6% versus 20.2%, P < 0.01) while use of carbamazepine was higher in the comparator group (15.4% versus 44.0%, P < 0.05). Multivariate logistic regression confirmed four factors associated with antiepileptic drug-induced psychotic disorder: female gender, temporal lobe involvement and use of levetiracetam, and a negative association with carbamazepine. Disorganized behaviours and thinking were more common in the antiepileptic drug-induced psychotic disorder group (100% versus 72.6% and 76.9% versus 38.1%, respectively; P < 0.05). The percentage of continuous treatment with antipsychotic drugs was lower in the antiepileptic drug-induced psychotic disorder group (15.4% versus 66.7%, P < 0.01). No patients experienced a chronic course in antiepileptic drug-induced psychotic disorder group whereas 40.5% did in non-antiepileptic drug induced psychotic disorder (P < 0.05). Our findings indicated that one in seven patients with epilepsy who developed psychosis had antiepileptic drug-induced psychotic disorder. In these patients, female gender, temporal lobe involvement and current use of levetiracetam were significantly associated with antiepileptic drug induced psychotic disorder compared to other types of psychosis, while carbamazepine had a negative association. Disorganized behaviours and thinking were predominant in antiepileptic drug-induced psychotic disorder. Patients with antiepileptic drug-induced psychotic disorder differed from non-antiepileptic drug-induced psychotic disorders in having better outcome.
抗癫痫药物治疗可能会使一些患者诱发精神病。然而,在癫痫学或精神病学的分类系统中,对于抗癫痫药物所致精神障碍,尚无公认的定义或诊断标准。在本研究中,我们调查了癫痫患者中抗癫痫药物所致精神障碍的临床谱。回顾了1993年1月至2015年6月在皇家墨尔本医院被神经精神科医生诊断为患有精神障碍的所有癫痫患者的病历。提取了有关癫痫及其治疗、精神症状特征和转归的数据。癫痫的诊断依据国际抗癫痫联盟的分类系统确定,而精神障碍的诊断则根据《精神疾病诊断与统计手册》第5版以及癫痫神经精神障碍的相关提议做出。将抗癫痫药物所致精神障碍患者与同期评估的与抗癫痫药物无关的精神障碍患者(非抗癫痫药物所致精神障碍组)进行比较。进行单因素比较,并选择P<0.1的变量进行多因素逻辑回归分析。筛查了2630例癫痫住院患者和门诊患者的病历,从中确定了98例(3.7%)患有精神障碍。其中,14例(14.3%)被诊断为抗癫痫药物所致精神障碍。排除1例丙戊酸盐撤药后出现精神病的患者,抗癫痫药物所致精神障碍组中76.9%为女性,且抗癫痫药物所致精神障碍组颞叶受累的比例更高(69.2%对38.1%,P<0.05)。抗癫痫药物所致精神障碍组左乙拉西坦的当前使用率更高(84.6%对20.2%,P<0.01),而比较组中卡马西平的使用率更高(15.4%对44.0%,P<0.05)。多因素逻辑回归确定了与抗癫痫药物所致精神障碍相关的四个因素:女性、颞叶受累、左乙拉西坦的使用,以及与卡马西平呈负相关。紊乱的行为和思维在抗癫痫药物所致精神障碍组中更为常见(分别为100%对72.6%和76.9%对38.1%;P<0.05)。抗癫痫药物所致精神障碍组使用抗精神病药物持续治疗的比例较低(15.4%对66.7%,P<0.01)。抗癫痫药物所致精神障碍组无患者经历慢性病程,而非抗癫痫药物所致精神障碍组有40.5%的患者经历慢性病程(P<0.05)。我们的研究结果表明,在出现精神病的癫痫患者中,七分之一患有抗癫痫药物所致精神障碍。在这些患者中,与其他类型的精神病相比,女性、颞叶受累和当前使用左乙拉西坦与抗癫痫药物所致精神障碍显著相关,而卡马西平呈负相关。紊乱的行为和思维在抗癫痫药物所致精神障碍中占主导。抗癫痫药物所致精神障碍患者与非抗癫痫药物所致精神障碍患者的转归不同,前者转归较好。