Richens A
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, UK.
Seizure. 1995 Sep;4(3):211-4. doi: 10.1016/s1059-1311(05)80063-9.
The development of assays for plasma antiepileptic drug concentrations has led to the discovery of many pharmacokinetic interactions, some causing drug intoxication and others resulting in ineffective drug concentrations. In the 1970s, a number of epileptologists began to argue that single drug therapy was desirable in the treatment of epilepsy and this has become the accepted policy when initiating therapy. About 75% of patients treated in this way will achieve remission with a minimum of adverse drug reactions. The remainder, however, continue to have unacceptable seizures and usually receive combinations of drugs. Evidence indicates that the response rate on adding a second drug is low, although in some studies of new drugs such as vigabatrin up to one-half of patients receiving add-on therapy experience a 50% or greater reduction in seizure frequency, and 10-15% are seizure-free in the short term. Unfortunately, randomized placebo-controlled studies have not been undertaken to compare the relative merits of monotherapy and combination therapy with respect of seizure control and adverse effects. It is argued that the time has come to do so, particularly in view of the known mode of action of some of the new drugs. Perhaps blocking excitation with one drug at the same time as enhancing inhibition with another may be better than doing only one or the other.
血浆抗癫痫药物浓度检测方法的发展促使人们发现了许多药代动力学相互作用，其中一些会导致药物中毒，另一些则会导致药物浓度无效。20世纪70年代，一些癫痫学家开始主张在癫痫治疗中采用单一药物治疗，这已成为起始治疗时被认可的策略。以这种方式治疗的患者中约75%将实现缓解，且药物不良反应最少。然而，其余患者仍有无法接受的癫痫发作，通常会接受联合用药。有证据表明，添加第二种药物后的缓解率较低，尽管在一些关于新药（如氨己烯酸）的研究中，高达一半接受附加治疗的患者癫痫发作频率降低了50%或更多，且10%至15%的患者在短期内无癫痫发作。不幸的是，尚未进行随机安慰剂对照研究来比较单一疗法和联合疗法在癫痫控制和不良反应方面的相对优点。有人认为现在是时候这样做了，特别是考虑到一些新药已知的作用方式。也许用一种药物阻断兴奋的同时用另一种药物增强抑制作用可能比只做其中一项更好。
