Kennedy Gina M, Lhatoo Samden D
Department of Neurology, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol, England.
CNS Drugs. 2008;22(9):739-60. doi: 10.2165/00023210-200822090-00003.
A variety of newer antiepileptic drugs (AEDs) are now available for treating patients with epilepsy in addition to the 'conventional' drugs that have been available throughout a large part of the last century. Since these drugs act to suppress the pathological neuronal hyperexcitability that constitutes the final substrate in many seizure disorders, it is not surprising that they are prone to causing adverse reactions that affect the CNS.Information on adverse effects of the older AEDs has been mainly observational. Equally, whilst the newer drugs have been more systematically studied, their long-term adverse effects are not clearly known. This is illustrated by the relatively late emergence of the knowledge of visual field constriction in the case of vigabatrin, which only became known after several hundred thousand patient-years of use. However, older drugs continue to be studied and there has been more recent comment on the possible effect of valproate (valproic acid) on cognition following exposure to this drug in utero.With most AEDs, there are mainly dose-related adverse effects that could be considered generic, such as sedation, drowsiness, incoordination, nausea and fatigue. Careful dose titration with small initial doses can reduce the likelihood of these adverse effects occurring. Adverse effects such as paraesthesiae are more commonly reported with drugs such as topiramate and zonisamide that have carbonic anhydrase activity. Weight loss and anorexia can also be peculiar to these drugs. Neuropsychiatric adverse effects are reported with a variety of AEDs and may not be dose related. Some drugs, such as carbamazepine when used to treat primary generalized epilepsy, can exacerbate certain seizure types. Rare adverse effects such as hyperammonaemia with valproate are drug specific. There are relatively very few head-to-head comparisons of AEDs and limited information is available in this regard.In this review, we discuss the available literature and provide a comprehensive summary of adverse drug reactions of AEDs affecting the CNS.
除了在上个世纪大部分时间里都已存在的“传统”药物外，现在还有多种新型抗癫痫药物（AEDs）可用于治疗癫痫患者。由于这些药物的作用是抑制构成许多癫痫疾病最终发病机制的病理性神经元过度兴奋，所以它们容易引起影响中枢神经系统的不良反应也就不足为奇了。关于 older AEDs 不良反应的信息主要来自观察性研究。同样，虽然新型药物得到了更系统的研究，但其长期不良反应尚不清楚。这一点在 vigabatrin 导致视野缩窄的情况中体现得较为明显，该情况在使用了几十万患者年之后才被发现。然而，对 older 药物的研究仍在继续，近期也有关于丙戊酸盐（丙戊酸）在子宫内接触后对认知可能产生影响的评论。
大多数 AEDs 主要有与剂量相关的不良反应，这些反应可被视为一般性的，如镇静、嗜睡、共济失调、恶心和疲劳。通过小剂量起始并仔细滴定剂量，可以降低这些不良反应发生的可能性。像托吡酯和唑尼沙胺这类具有碳酸酐酶活性的药物，更常出现如感觉异常等不良反应。体重减轻和厌食也可能是这些药物特有的。多种 AEDs 都有神经精神方面的不良反应报告，且可能与剂量无关。有些药物，如卡马西平用于治疗原发性全身性癫痫时，可能会加重某些癫痫发作类型。像丙戊酸盐导致高氨血症这样的罕见不良反应则是特定药物所特有的。AEDs 之间相对很少有直接对比研究，这方面的信息有限。
在本综述中，我们讨论了现有文献，并对影响中枢神经系统的 AEDs 药物不良反应进行了全面总结。
