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20世纪90年代癫痫的管理。未来研究的进展、不确定性和优先事项。

The management of epilepsy in the 1990s. Acquisitions, uncertainties and priorities for future research.

作者信息

Beghi E, Perucca E

机构信息

Mario Negri Institute for Pharmacological Research, Milan, Italy.

出版信息

Drugs. 1995 May;49(5):680-94. doi: 10.2165/00003495-199549050-00004.

Abstract

The pharmacological treatment of epilepsy has made considerable progress during the last decade, due to improved knowledge of the clinical pharmacology of individual drugs, acquisition of new information on the factors affecting response and need for drug treatment, and development of promising new agents. Once a clinical diagnosis of epilepsy has been made (which generally requires the occurrence of more than one seizure), treatment should be started with a single drug selected on the basis of seizure type and tolerability profile. Although there are important regional differences in prescribing patterns and individual circumstances may dictate alternative choices, carbamazepine is generally regarded as the preferred treatment for partial seizures (with or without secondary generalisation) while valproic acid (sodium valproate) is usually the first choice in most forms of generalised epilepsies. To achieve therapeutic success, the daily dosage must be tailored to meet individual needs, and there is suggestive evidence that in some patients the dosage prescribed initially may be unnecessarily large. Plasma antiepileptic drug concentrations may aid in the individualization of dosage, but should not be regarded as a substitute for careful monitoring of clinical response. Although overall about 70% of patients can be completely controlled, response rate is influenced by a number of factors, the most important of which are seizure type and syndromic form. The importance of a correct syndromic classification for rational drug selection has been poorly assessed and represents a major area for future research. Patients who do not respond to the highest tolerated dose of the initially prescribed drug may be switched to monotherapy with an alternative agent or may be given add-on treatment with a second drug. Appropriate prospective trials are required to assess the merits of either strategy. If add-on therapy is selected and the patient becomes seizure free, it may be possible to discontinue the drug prescribed initially and reinstitute monotherapy. Only a minority of patients are likely to require multiple drug therapy, and it remains to be established whether specific drug combinations are more effective than others. Until further information becomes available, the new agents should be reserved for patients failing to respond to the conventional treatments of first choice. Patients whose seizures cannot be controlled by available drugs should be reassessed, and polytherapy should be maintained only when there is clear evidence that benefits outweigh possible adverse effects. In many patients who have been seizure free for at least 2 years it may be possible to gradually discontinue all medications.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

在过去十年中,癫痫的药物治疗取得了显著进展,这得益于对各药物临床药理学的深入了解、获取了有关影响药物治疗反应及需求因素的新信息,以及有前景的新药物的研发。一旦做出癫痫的临床诊断(通常需要发作不止一次),治疗应从根据发作类型和耐受性选择的单一药物开始。尽管处方模式存在重要的地区差异,且个体情况可能决定其他选择,但卡马西平通常被视为部分性发作(伴或不伴继发全面性发作)的首选治疗药物,而丙戊酸(丙戊酸钠)通常是大多数类型全身性癫痫的首选药物。为取得治疗成功,每日剂量必须根据个体需求进行调整,有迹象表明,在一些患者中,最初开具的剂量可能过大。血浆抗癫痫药物浓度有助于剂量个体化,但不应被视为替代对临床反应的仔细监测。尽管总体上约70%的患者可得到完全控制,但反应率受多种因素影响,其中最重要的是发作类型和综合征形式。正确的综合征分类对合理选药的重要性尚未得到充分评估,这是未来研究的一个主要领域。对最初开具的药物最高耐受剂量无反应的患者,可换用另一种药物进行单药治疗,或加用第二种药物进行联合治疗。需要进行适当的前瞻性试验来评估这两种策略的优缺点。如果选择联合治疗且患者不再发作,可能可以停用最初开具的药物并恢复单药治疗。只有少数患者可能需要联合用药,特定药物组合是否比其他组合更有效仍有待确定。在有更多信息可用之前,新药物应保留给对首选传统治疗无反应的患者。癫痫发作无法用现有药物控制的患者应重新评估,只有在有明确证据表明益处大于可能的不良反应时才应维持联合治疗。在许多至少两年无癫痫发作的患者中,有可能逐渐停用所有药物。(摘要截选至400字)

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