Research Department of Practice and Policy, University College London School of Pharmacy, London, UK; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, China.
Department of Paediatrics and Psychiatry, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia; Murdoch Children's Research Institute, Melbourne, VIC, Australia.
Lancet Child Adolesc Health. 2020 Jun;4(6):435-443. doi: 10.1016/S2352-4642(20)30100-0.
Individuals with attention-deficit hyperactivity disorder (ADHD) are at increased risk of seizures. Stimulant medications such as methylphenidate are the most commonly prescribed treatment for ADHD, but the association between their therapeutic use and the risk of seizures is unclear. We aimed to investigate the association between methylphenidate treatment and the risk of seizure.
For this population-based observational study, we used the electronic medical record database of the Hong Kong Clinical Data Analysis And Reporting System to identify individuals aged 6-25 years who received at least one methylphenidate prescription during the study period. Individuals with records of seizure or epilepsy before the study period were excluded. Individuals treated with methylphenidate who had seizures during the study period were included in the subsequent analyses, and a self-controlled case-series design was used to control for time-invariant individual characteristics. We did additional analyses using skin infection as a negative control outcome. We compared relative incidence of seizure during periods when individuals were exposed to methylphenidate with that during non-exposed periods.
Of 29 604 individuals prescribed methylphenidate between Jan 1, 2001, and Dec 31, 2017, 269 (199 males and 70 females) had incident seizures. The mean age at baseline was 6·66 years (SD 2·01) and the median age at the incident seizure was 9·69 years (IQR 7·62-12·99). The overall incidence of seizure during methylphenidate treatment was 4·4 per 10 000 patient-years. We detected an increased risk of seizure during the first 30 days of methylphenidate treatment compared with that during non-exposed periods, with an incidence rate ratio of 4·01 (95% CI 2·09-7·68). No increase in risk was identified during the following 31-180 days of treatment (1·13, 0·56-2·25) or during subsequent treatment (1·38, 0·92-2·07). We did not identify an increased risk in any risk window for the negative control outcome analysis. No individuals died because of a seizure during the study period.
The incidence of seizures was higher in the period immediately after the start of methylphenidate treatment than in the non-exposed period. No increased risk was observed during continuation of methylphenidate treatment. The association between methylphenidate treatment and seizures immediately after initiation of medication can be seen as a potential safety signal. Monitoring of neurological outcomes in individuals with ADHD is recommended when they first start methylphenidate treatment.
Hong Kong Research Grants Council.
患有注意力缺陷多动障碍（ADHD）的个体癫痫发作的风险增加。哌醋甲酯等兴奋剂类药物是 ADHD 最常开的治疗药物，但它们的治疗使用与癫痫发作风险之间的关系尚不清楚。我们旨在研究哌醋甲酯治疗与癫痫发作风险之间的关系。
在这项基于人群的观察性研究中，我们使用香港临床数据分析及报告系统的电子病历数据库，确定了在研究期间至少接受过一次哌醋甲酯处方的 6-25 岁个体。研究前有癫痫或癫痫记录的个体被排除在外。在研究期间接受哌醋甲酯治疗且发生癫痫发作的个体被纳入后续分析，并使用自身对照病例系列设计来控制个体不变的特征。我们还使用皮肤感染作为阴性对照结果进行了额外分析。我们比较了个体接受哌醋甲酯治疗期间和未治疗期间癫痫发作的相对发生率。
在 2001 年 1 月 1 日至 2017 年 12 月 31 日期间，共开具了 29604 份哌醋甲酯处方，其中 269 名（199 名男性和 70 名女性）发生了癫痫发作。基线时的平均年龄为 6.66 岁（SD 2.01），癫痫发作的中位年龄为 9.69 岁（IQR 7.62-12.99）。哌醋甲酯治疗期间的总体癫痫发作发生率为每 10000 患者年 4.4 例。与未治疗期间相比，我们发现哌醋甲酯治疗的前 30 天内癫痫发作的风险增加，发病率比为 4.01（95%CI 2.09-7.68）。在接下来的 31-180 天的治疗期间（1.13，0.56-2.25）或随后的治疗期间（1.38，0.92-2.07），未发现风险增加。在阴性对照结果分析的任何风险窗口中，均未发现风险增加。在研究期间，没有个体因癫痫发作而死亡。
在开始哌醋甲酯治疗后的立即时期，癫痫发作的发生率高于未治疗时期。在继续使用哌醋甲酯治疗期间，未发现风险增加。在开始药物治疗后立即出现的哌醋甲酯治疗与癫痫发作之间的关联可以被视为一个潜在的安全信号。建议在 ADHD 个体首次开始使用哌醋甲酯治疗时，监测其神经学结局。
香港研究资助局。
