Eckert Anne
Neurobiologisches Labor für Brain Aging and Mental Health, Universitäre Psychiatrische Kliniken Basel, Basel.
Ther Umsch. 2009 Jun;66(6):485-92. doi: 10.1024/0040-5930.66.6.485.
Because antidepressants and antipsychotics are commonly described in combination with drugs used to treat comorbid psychiatric or somatic disorders (e.g. anxiolytics, mood stabilizers, cardiovascular drugs, antimicrobial agents), they may be involved in drug interactions. Furthermore, agents such as lithium and atypical antipsychotics may be used to augment the antidepressant response in cases of refractory depression. Based on their mechanisms, drug-drug interactions can be classified either as pharmacokinetic or pharmacodynamic in nature. The well-documented risk of potentially harmful pharmacodynamic drug interactions with first-generation anti-depressants, e.g. monoamine oxidase inhibitors (MAOIs), with regard to the induction of the serotonin syndrome, has contributed to a gradual decline in their use in clinical practise. Second- and third-generation antidepressants have gradually replaced tricyclic antidepressants (TCAs) and MAOIs, mainly because of their improved tolerability and safety profile. The second- and third-generation antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and other compounds with different mechanisms of action. These drugs and also the majority of antipsychotics are metabolized in the liver by the cytochrome P450 (CYP) enzyme system. Therefore, the use of these compounds may be associated with clinically relevant pharmacokinetic interactions with other medications. The knowledge about the CYP metabolism of drugs may be used to guide the selection of an antidepressant or an anti-psychotic with a low drug-drug interaction potential for an individual patient. The aim of the present article is to review drug-interaction potentials with specific focus on second-generation antidepressants (SSRIs), newer antidepressants (SNRIs: venlafaxine and duloxetine; bupropion, mirtazapine, trazodone), novel atypical antidepressants (agomelatine), as well as new generation atypical antipsychotics (aripiprazole, paliperidone).
由于抗抑郁药和抗精神病药通常与用于治疗共病精神或躯体疾病的药物(如抗焦虑药、心境稳定剂、心血管药物、抗菌药物)联合使用,它们可能会涉及药物相互作用。此外,锂盐和非典型抗精神病药等药物可用于增强难治性抑郁症患者的抗抑郁反应。根据其作用机制,药物相互作用可分为药代动力学或药效学性质。第一代抗抑郁药(如单胺氧化酶抑制剂(MAOIs))在诱发血清素综合征方面存在充分记录的潜在有害药效学药物相互作用风险,这导致其在临床实践中的使用逐渐减少。第二代和第三代抗抑郁药已逐渐取代三环类抗抑郁药(TCAs)和MAOIs,主要是因为它们的耐受性和安全性有所改善。第二代和第三代抗抑郁药包括选择性5-羟色胺再摄取抑制剂(SSRIs)、5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRIs)以及其他作用机制不同的化合物。这些药物以及大多数抗精神病药在肝脏中通过细胞色素P450(CYP)酶系统进行代谢。因此,使用这些化合物可能会与其他药物发生具有临床相关性的药代动力学相互作用。关于药物CYP代谢的知识可用于指导为个体患者选择具有低药物相互作用潜力的抗抑郁药或抗精神病药。本文的目的是回顾药物相互作用潜力,特别关注第二代抗抑郁药(SSRIs)、新型抗抑郁药(SNRIs:文拉法辛和度洛西汀;安非他酮、米氮平、曲唑酮)、新型非典型抗抑郁药(阿戈美拉汀)以及新一代非典型抗精神病药(阿立哌唑、帕利哌酮)。