Adams Jesse, Alipio-Jocson Valerie, Inoyama Katherine, Bartlett Victoria, Sandhu Saira, Oso Jemima, Barry John J, Loring David W, Meador Kimford J
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, U.S.A.
Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, U.S.A.
Epilepsia. 2017 Dec;58(12):2124-2132. doi: 10.1111/epi.13917. Epub 2017 Oct 9.
Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study.
Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently.
Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect sizes were moderate to large. Comparisons with untreated controls (n = 14) revealed greater improvement for epilepsy patients on omissions and commissions, with improvement trends on d' and hits. Seizure frequency did not increase with methylphenidate treatment (2.8/month vs. 2.4/month).
Methylphenidate may be an effective and safe option for improving cognition and quality of life in epilepsy. Larger and longer double-blind, placebo-controlled clinical trials are needed.
认知困难在癫痫患者中很常见。除了减少癫痫发作和调整抗癫痫药物外，成人中尚无经过充分验证的治疗方法。哌甲酯在患有癫痫和注意力缺陷多动障碍的儿童中有效使用，但其在成人中的效果尚未得到系统评估。我们假设哌甲酯可以安全地改善成年癫痫患者的认知能力。在此，我们详细介绍一项双盲、安慰剂对照、单剂量研究的开放标签随访情况。
30名癫痫患者在双盲阶段后进入为期1个月的哌甲酯开放标签试验。剂量根据临床实践和患者耐受性进行滴定，范围为20 - 40毫克/天。主要测量指标包括：康纳斯连续操作测验（CPT）、符号数字模式测验（SDMT）和佐治亚医学院记忆测验（MCG）。次要测量指标包括：贝克抑郁量表第二版（BDI-II）、贝克焦虑量表、淡漠评估量表（AES）、兴奋剂副作用清单、不良事件概况、癫痫患者生活质量-89量表（QOLIE-89）以及癫痫发作频率。同时对14名健康、未用药的对照者进行了测试。
28名癫痫参与者（13名男性/15名女性）完成了试验。因焦虑（n = 1）和疲劳（n = 1）出现退出情况。平均年龄为36.4岁（范围 = 20 - 60岁）。癫痫类型为：局灶性（n = 21）、全身性（n = 6）或未分类（n = 1）。平均癫痫病程为12.3年。平均基线癫痫发作频率为每月2.8次。哌甲酯治疗后，SDMT、MCG、CPT（区分目标与非目标的能力[d']、命中次数、命中反应时间标准差、遗漏次数和错误次数）以及QOLIE子量表（精力/疲劳、注意力/集中力、记忆力和语言能力；配对t检验；p≤0.002）有显著改善。BDI-II和其他子量表也有改善，但统计学意义较低。效应大小为中等至较大。与未治疗的对照者（n = 14）相比，癫痫患者在遗漏次数和错误次数方面改善更大，在d'和命中次数方面有改善趋势。哌甲酯治疗后癫痫发作频率未增加（每月2.8次对每月2.4次）。
哌甲酯可能是改善癫痫患者认知和生活质量的一种有效且安全的选择。需要进行更大规模、更长时间的双盲、安慰剂对照临床试验。
