Pisani F, Spina E, Oteri G
Institute of Neurological and Neurosurgical Sciences, First Neurological Clinic, Messina, Italy.
Epilepsia. 1999;40 Suppl 10:S48-56. doi: 10.1111/j.1528-1157.1999.tb00885.x.
The use of antidepressant drugs (ADs) in patients with epilepsy still raises uncertainties because of the widespread conviction that this class of drugs facilitates seizures. A detailed knowledge of this issue in its various aspects may help in optimal management of patients suffering concurrently from epilepsy and depression. This article reviews the available data in vitro in animals and humans concerning the known potential of various ADs to induce epileptic seizures. Emphasis has been placed on those variables that may generate confusion in interpreting the results of the various studies. Most ADs at therapeutic dosages exhibit in nonepileptic patients a seizure risk close to that reported for the first spontaneous seizure in the general population (i.e., <0.1%). In patients taking high AD doses, seizure incidence rises markedly and may reach values up to 40%. With a patient history of epilepsy and/or concomitant drugs that act on neuronal excitability, low or therapeutic AD doses may be sufficient to trigger seizures. Experimental data are in partial conflict with human data on the relative potential seizure risk of the various ADs. Therefore, a reliable scale for assigning a relative value to an individual AD or to single AD classes cannot be made. It appears fair to say that maprotiline and amoxapine exhibit the greatest seizure risk, whereas trazodone, fluoxetine, and fluvoxamine exhibit the least. Some ADs may also display antiepileptic effects, especially in low doses, in experimental models of epilepsy and in humans, but the mechanism of this action is largely unknown. The available data suggest that ADs may display both convulsant and anticonvulsant effects and that the most important factor in determining the direction of a given compound in terms of excitation/inhibition is drug dosage. It is probable that drugs that increase serotonergic transmission are less convulsant or, even, more anticonvulsant than others. Because of mutual pharmacokinetic interactions between antiepileptic drugs and ADs, with consequent marked changes in plasma concentrations, it remains to be established whether or not plasma AD levels that are effective against depression also facilitate seizures. Finally, exploring the mechanisms through which ADs modulate neuronal excitability might open new possibilities in antiepileptic drug development.
在癫痫患者中使用抗抑郁药物（ADs）仍存在不确定性，因为人们普遍认为这类药物会诱发癫痫发作。全面了解这一问题的各个方面，可能有助于对同时患有癫痫和抑郁症的患者进行最佳管理。本文综述了在动物和人体上进行的体外实验数据，这些数据涉及各种抗抑郁药物诱发癫痫发作的已知可能性。重点关注了那些可能在解释各项研究结果时产生混淆的变量。大多数抗抑郁药物在治疗剂量下，在非癫痫患者中引发癫痫发作的风险接近一般人群首次自发性癫痫发作的报告风险（即<0.1%）。在服用高剂量抗抑郁药物的患者中，癫痫发作发生率显著上升，可能高达40%。对于有癫痫病史和/或同时服用作用于神经元兴奋性药物的患者，低剂量或治疗剂量的抗抑郁药物可能就足以引发癫痫发作。关于各种抗抑郁药物相对癫痫发作风险的实验数据与人体数据存在部分冲突。因此，无法制定一个可靠的量表来为个体抗抑郁药物或单一抗抑郁药物类别赋予相对值。可以公平地说，马普替林和阿莫沙平表现出最大的癫痫发作风险，而曲唑酮、氟西汀和氟伏沙明表现出最小的风险。一些抗抑郁药物在癫痫实验模型和人体中，尤其是低剂量时，也可能表现出抗癫痫作用，但其作用机制大多未知。现有数据表明，抗抑郁药物可能同时具有惊厥和抗惊厥作用，而就兴奋/抑制而言，决定给定化合物作用方向的最重要因素是药物剂量。增加5-羟色胺能传递的药物可能比其他药物惊厥性更低，甚至抗惊厥性更强。由于抗癫痫药物和抗抑郁药物之间存在相互的药代动力学相互作用，导致血浆浓度显著变化，对于有效治疗抑郁症的血浆抗抑郁药物水平是否也会诱发癫痫发作，仍有待确定。最后，探索抗抑郁药物调节神经元兴奋性的机制可能为抗癫痫药物的研发开辟新的可能性。
