Johannessen Landmark Cecilie
Department of Pharmacy, Faculty of Health Sciences, Oslo University College, Oslo, Norway.
CNS Drugs. 2008;22(1):27-47. doi: 10.2165/00023210-200822010-00003.
Antiepileptic drugs (AEDs) are used extensively to treat multiple non-epilepsy disorders, both in neurology and psychiatry. This article provides a review of the clinical efficacy of AEDs in non-epilepsy disorders based on recently published preclinical and clinical studies, and attempts to relate this efficacy to the mechanism of action of AEDs and pathophysiological processes associated with the disorders. Some newer indications for AEDs have been established, while others are under investigation. The disorders where AEDs have been demonstrated to be of clinical importance include neurological disorders, such as essential tremor, neuropathic pain and migraine, and psychiatric disorders, including anxiety, schizophrenia and bipolar disorder. Many of the AEDs have various targets of action in the synapse and have several proposed relevant mechanisms of action in epilepsy and in other disorders. Pathophysiological processes disturb neuronal excitability by modulating ion channels, receptors and intracellular signalling pathways, and these are targets for the pharmacological action of various AEDs. Attention is focused on the glutamatergic and GABAergic synapses. In psychiatric conditions such as schizophrenia and bipolar disorder, AEDs such as valproate, carbamazepine and lamotrigine appear to have clear roles based on their effect on intracellular pathways. On the other hand, some AEDs, e.g. topiramate, have efficacy for nonpsychiatric disorders including migraine, possibly by enhancing GABAergic and reducing glutamatergic neurotransmission. AEDs that seem to enhance GABAergic neurotransmission, e.g. tiagabine, valproate, gabapentin and possibly levetiracetam, may have a role in treating neurological disorders such as essential tremor, or anxiety disorders. AEDs with effects on voltage-gated sodium or calcium channels may be advantageous in treating neuropathic pain, e.g. gabapentin, pregabalin, carbamazepine, oxcarbazepine, lamotrigine and valproate. Co-morbid conditions associated with epilepsy, such as mood disorders and migraine, may often respond to treatment with AEDs. Other possible disorders where AEDs may be of clinical importance include cancer, HIV infection, drug and alcohol abuse, and also in neuroprotection. A future challenge is to evaluate the second-generation AEDs in non-epilepsy disorders and to design clinical trials to study their effects in such disorders in paediatric patients. Differentiation between the main mechanisms of action of the AEDs needs more consideration in drug selection for tailored treatment of the various non-epilepsy disorders.
抗癫痫药物（AEDs）被广泛用于治疗神经科和精神科的多种非癫痫性疾病。本文基于最近发表的临床前和临床研究，综述了AEDs在非癫痫性疾病中的临床疗效，并试图将这种疗效与AEDs的作用机制以及与这些疾病相关的病理生理过程联系起来。AEDs的一些新适应症已经确立，而其他一些仍在研究中。已证明AEDs具有临床重要性的疾病包括神经系统疾病，如特发性震颤、神经性疼痛和偏头痛，以及精神疾病，包括焦虑症、精神分裂症和双相情感障碍。许多AEDs在突触中有多种作用靶点，并且在癫痫和其他疾病中有几种提出的相关作用机制。病理生理过程通过调节离子通道、受体和细胞内信号通路来干扰神经元兴奋性，而这些是各种AEDs药理作用的靶点。注意力集中在谷氨酸能和γ-氨基丁酸能突触上。在精神疾病如精神分裂症和双相情感障碍中，丙戊酸盐、卡马西平和拉莫三嗪等AEDs基于其对细胞内通路的作用似乎具有明确的作用。另一方面，一些AEDs，如托吡酯，对包括偏头痛在内的非精神疾病有效，可能是通过增强γ-氨基丁酸能和减少谷氨酸能神经传递。似乎增强γ-氨基丁酸能神经传递的AEDs，如替加宾、丙戊酸盐、加巴喷丁以及可能的左乙拉西坦，可能在治疗特发性震颤等神经系统疾病或焦虑症中发挥作用。对电压门控钠通道或钙通道有作用的AEDs在治疗神经性疼痛方面可能具有优势，如加巴喷丁、普瑞巴林、卡马西平、奥卡西平、拉莫三嗪和丙戊酸盐。与癫痫相关的共病情况，如情绪障碍和偏头痛，通常可能对AEDs治疗有反应。AEDs可能具有临床重要性的其他可能疾病包括癌症、HIV感染、药物和酒精滥用，以及神经保护。未来的一个挑战是评估第二代AEDs在非癫痫性疾病中的作用，并设计临床试验来研究它们在儿科患者此类疾病中的效果。在为各种非癫痫性疾病进行个体化治疗选择药物时，需要更多考虑AEDs主要作用机制之间的差异。
