Monaco F, Cicolin A
Neurological Clinic, Università Amedeo Avogadro del Piemonte Orientale, Novara, Italy.
Epilepsia. 1999;40 Suppl 10:S71-6. doi: 10.1111/j.1528-1157.1999.tb00888.x.
This review considers the relevance of pharmacokinetic interactions between antiepileptic drugs (AEDs) and psychoactive drugs in the treatment of mood disorders in patients with epilepsy. The determination of plasma levels of some of these drugs (mainly the AEDs) has enabled clinicians to evaluate the kinetic modifications during the course of such combined therapies and to adjusting the dosages in cases of subtherapeutic or toxic levels. In general, phenobarbital, phenytoin, and carbamazepine stimulate the catabolic degradation of tricyclic antidepressants (TCAs), and TCAs have an inhibitory effect on the elimination of AEDs. The newer antidepressants that selectively inhibit the reuptake of serotonin (SSRIs), although in different fashions for the different substances (fluoxetine, fluvoxamine, paroxetine) may cause an increase of plasma AED levels through inhibition of the isoenzyme P450 2D6. Similarly, antipsychotics (APs) are more rapidly metabolized when AEDs are co-administered, whereas AED metabolism is scarcely influenced by AP. Finally, plasma levels of tranquilizers are lowered by AED co-therapy. As the concomitant administration of AED and psychoactive drugs becomes increasingly used for treatment of mood disorders in patients with or without epilepsy, therapeutic drug monitoring may be useful in designing correct and rational therapy.
本综述探讨了抗癫痫药物（AEDs）与精神活性药物之间的药代动力学相互作用在癫痫患者情绪障碍治疗中的相关性。对其中一些药物（主要是AEDs）血浆水平的测定，使临床医生能够评估联合治疗过程中的动力学变化，并在血药浓度低于治疗水平或出现毒性水平时调整剂量。一般来说，苯巴比妥、苯妥英和卡马西平会刺激三环类抗抑郁药（TCAs）的分解代谢，而TCAs对AEDs的消除有抑制作用。新型选择性5-羟色胺再摄取抑制剂（SSRIs）类抗抑郁药，尽管不同药物（氟西汀、氟伏沙明、帕罗西汀）的作用方式不同，但可能通过抑制同工酶P450 2D6导致血浆AEDs水平升高。同样，联合使用AEDs时，抗精神病药物（APs）的代谢更快，而AP对AEDs代谢的影响很小。最后，联合使用AEDs会降低镇静剂的血浆水平。由于越来越多地同时使用AEDs和精神活性药物来治疗癫痫患者或非癫痫患者的情绪障碍，治疗药物监测可能有助于制定正确合理的治疗方案。
