Regional Health Agency of Tuscany, Firenze, Italy.
Department of Internal Medicine and Therapeutics, Clinical and Experimental Pharmacology Unit, University of Pavia, Pavia, Italy.
Curr Neuropharmacol. 2023;21(8):1666-1690. doi: 10.2174/1570159X20666220524121645.
Antiseizure medications and drugs for psychiatric diseases are frequently used in combination. In this context, pharmacokinetic interactions between these drugs may occur. The vast majority of these interactions are primarily observed at a metabolic level and result from changes in the activity of the cytochrome P450 (CYP). Carbamazepine, phenytoin, and barbiturates induce the oxidative biotransformation and can consequently reduce the plasma concentrations of tricyclic antidepressants, many typical and atypical antipsychotics and some benzodiazepines. Newer antiseizure medications show a lower potential for clinically relevant interactions with drugs for psychiatric disease. The pharmacokinetics of many antiseizure medications is not influenced by antipsychotics and anxiolytics, while some newer antidepressants, namely fluoxetine, fluvoxamine and viloxazine, may inhibit CYP enzymes leading to increased serum concentrations of some antiseizure medications, including phenytoin and carbamazepine. Clinically relevant pharmacokinetic interactions may be anticipated by knowledge of CYP enzymes involved in the biotransformation of individual medications and of the influence of the specific comedication on the activity of these CYP enzymes. As a general rule, these interactions can be managed by careful evaluation of clinical response and, when indicated, individualized dosage adjustments guided by measurement of drugs serum concentrations, especially if pharmacokinetic interactions may cause any change in seizure control or signs of toxicity. Further studies are required to improve predictions of pharmacokinetic interactions between antiseizure medications and drugs for psychiatric diseases providing practical helps for clinicians in the clinical setting.
抗癫痫药物和精神疾病药物经常联合使用。在这种情况下，这些药物之间可能会发生药代动力学相互作用。这些相互作用绝大多数主要发生在代谢水平上，是由于细胞色素 P450（CYP）的活性变化引起的。卡马西平、苯妥英和巴比妥酸盐诱导氧化生物转化，从而降低三环类抗抑郁药、许多典型和非典型抗精神病药和一些苯二氮䓬类药物的血浆浓度。新型抗癫痫药物与精神疾病药物发生具有临床相关性相互作用的潜力较低。许多抗癫痫药物的药代动力学不受抗精神病药和抗焦虑药的影响，而一些新型抗抑郁药，如氟西汀、氟伏沙明和维洛沙嗪，可能会抑制 CYP 酶，导致一些抗癫痫药物（包括苯妥英和卡马西平）的血清浓度升高。通过了解个体药物生物转化中涉及的 CYP 酶以及特定合并用药对这些 CYP 酶活性的影响，可以预测具有临床相关性的药代动力学相互作用。一般来说，如果药代动力学相互作用可能导致癫痫控制或毒性迹象发生任何变化，可通过仔细评估临床反应，并在必要时根据药物血清浓度测量来进行个体化剂量调整来管理这些相互作用。需要进一步研究来改善抗癫痫药物和精神疾病药物之间药代动力学相互作用的预测，为临床医生在临床环境中提供实际帮助。
