Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida.
Department of Pharmacoepidemiology, Merck & Co. Inc, West Point, Pennsylvania.
Pharmacotherapy. 2020 May;40(5):455-468. doi: 10.1002/phar.2382. Epub 2020 Mar 23.
Among pharmacodynamic and pharmacokinetic drug-drug interactions (DDIs), psychotropic drug-drug interactions (pDDIs) are of particular interest because psychopharmacologic agents mark one of the fastest growing therapeutic drug classes over the past 2 decades, and prescribing multiple psychotropic drugs has become increasingly prevalent in clinical practice. However, the documentation of pDDIs across drug references has lacked consistency. Thus we set out to review the primary evidence directly supporting 58 pDDIs that were uniformly reported as "major" or "contraindicated" in three prominent drug references: Clinical Pharmacology, Micromedex, and Lexicomp. We identified 134 citations from Micromedex in December 2017 and 4251 citations from Medline in March 2018 involving any of the 58 pDDIs. The included articles directly observed a clinical adverse effect or effects on drug plasma concentrations from the concomitant use of the two listed drugs in each pDDI. These articles were classified as controlled studies (e.g., randomized controlled trials, clinical trials, or observational studies) or uncontrolled studies (case reports). A total of 124 studies with 2716 patients were included in this review. Commonly evaluated adverse effects related to the studied pDDIs included decreased effectiveness, central nervous system depression, neurotoxicity, QT-interval prolongation, and serotonin syndrome. Among the 58 pDDIs, 18 (31%) were not supported by any primary studies. Among the remaining 35 pDDIs supported by studies on clinical adverse effects, only 14 (40%) included evidence from controlled study designs. Only 7 (12.1%) of the 58 pDDIs had evidence from studies with a combined sample size of more than 100 patients. This literature review highlights the poor quality of evidence supporting major or contraindicated psychotropic DDI warnings. Most DDIs lacked support from controlled studies that evaluated clinically significant adverse effects, leaving uncertainty about the clinical relevance of the warning. More postmarketing studies are needed to evaluate the safety of psychotropic combination therapy.
在药效学和药代动力学药物相互作用（DDI）中，精神药物相互作用（pDDI）特别值得关注，因为在过去 20 年中，精神药理学药物是增长最快的治疗药物类别之一，并且在临床实践中，开多种精神药物越来越普遍。然而，药物参考资料中 pDDI 的记录缺乏一致性。因此，我们着手审查直接支持在三个著名药物参考资料中统一报告为“主要”或“禁忌”的 58 种 pDDI 的主要证据：临床药理学，Micromedex 和 Lexicomp。我们于 2017 年 12 月从 Micromedex 中确定了 134 条引文，并于 2018 年 3 月从 Medline 中确定了 4251 条引文，涉及 58 种 pDDI 中的任何一种。纳入的文章直接观察到两种列出的药物同时使用时产生的临床不良影响或对药物血浆浓度的影响。这些文章被归类为对照研究（例如，随机对照试验，临床试验或观察性研究）或非对照研究（病例报告）。这项综述共纳入了 124 项研究，共 2716 名患者。与所研究的 pDDI 相关的常用评估不良影响包括有效性降低，中枢神经系统抑制，神经毒性，QT 间期延长和血清素综合征。在 58 种 pDDI 中，有 18 种（31％）没有任何主要研究支持。在其余 35 种由临床不良影响研究支持的 pDDI 中，只有 14 种（40％）包括对照研究设计的证据。在 58 种 pDDI 中，仅有 7 种（12.1％）具有来自超过 100 名患者的合并样本量研究的证据。这项文献综述突出了支持主要或禁忌精神药物 DDI 警告的证据质量差。大多数 DDI 缺乏评估临床显着不良影响的对照研究支持，这使得有关警告的临床相关性存在不确定性。需要进行更多的上市后研究，以评估精神药物联合治疗的安全性。
