Sidhu Harpreet S, Sadhotra Akshay
Pharmacology, Maharishi Markandeshwar University Ambala, India.
Front Pharmacol. 2016 Aug 25;7:276. doi: 10.3389/fphar.2016.00276. eCollection 2016.
Antiepileptic drugs (AEDs) are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine, and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia, and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer's Lyrica become the market leading brand by 2018. In this review, we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder should be withdrawal from randomized placebo trials rather than open-label studies; otherwise this may lead to off-label uses of drug. The purpose of the present review is to relate the various mechanisms of action of new AEDs to pathophysiological mechanisms and clinical efficacy in neuropathic pain and migraine.
抗癫痫药物（AEDs）在全球范围内被广泛用于治疗癫痫以外的多种疾病，如神经性疼痛、偏头痛和双相情感障碍。由于这种情况，最近市场上已推出20多种新型第三代AEDs。新型AEDs的未来设计还必须有帮助治疗非癫痫性疾病的潜力。第二代AEDs在治疗各种非癫痫性疾病方面的广泛接受导致了市场上仿制药的出现。已批准的AEDs在癫痫以外的广泛使用既有经济原因，也有科学原因。双相情感障碍、偏头痛预防、纤维肌痛和神经性疼痛是抗惊厥药物开发者最具吸引力的适应症扩展机会，能带来巨额收入。非癫痫疾病的强劲增长将使辉瑞公司的普瑞巴林到2018年成为市场领先品牌。在本综述中，我们主要关注新型AEDs在治疗慢性疼痛和偏头痛预防方面的现状。AEDs具有强大的镇痛潜力，这在卡马西平广泛用于治疗三叉神经痛和丙戊酸钠广泛用于预防偏头痛中得到了证明。目前，关于新型AEDs用于非癫痫性疾病的数据尚无定论。并非所有AEDs在治疗神经性疼痛和偏头痛方面都有效。只有那些作用机制与疾病病理生理学相匹配的AEDs才有在非癫痫性疾病中显示疗效的潜力。因此，在启动临床前和临床试验之前，更好地了解疾病的病理生理学和新型AEDs的作用机制是必不可少的要求。许多新型AEDs在动物模型和开放标签研究中显示出良好的结果，但在随机、安慰剂对照试验中未能提供有力证据。关于特定AEDs在特定非癫痫性疾病中的临床疗效的最终决定应该来自随机安慰剂试验，而不是开放标签研究；否则这可能导致药物的标签外使用。本综述的目的是将新型AEDs的各种作用机制与神经性疼痛和偏头痛的病理生理机制及临床疗效联系起来。
