Department of Psychiatry and Behavioral Sciences, Harborview Medical Center, University of Washington, Seattle, WA, USA.
Int J Psychiatry Med. 2020 Mar;55(2):82-104. doi: 10.1177/0091217419870669. Epub 2019 Aug 30.
To assess the relative prevalence and factors affecting the prescription of medication combinations with a theoretical efficacy limiting pharmacodynamic interaction, defined as two medications with opposing indications and side effects or antagonistic action at the primary receptor of mechanism of action.
One hundred sixteen combinations were identified for 10 types of pharmacodynamic interactions. PubMed was searched for each combination to assess the quality of evidence either supporting clinical use or verifying reduced efficacy. Micromedex was searched to determine the presence of warnings to prescribers of reduced efficacy. The prevalence in clinical practice was determined by computer review of the Genoa Healthcare database for all prescribers at 10 participating community mental health centers. The expected prevalence was calculated as the product of the probability of each medication prescribed alone and was compared with the actual prevalence of the combination using the test of proportions.
The frequency of prescription of eight combinations met the Bonferroni corrected level of significance of p < 0.001. Four were combinations of amphetamine and D2 antagonists and each were prescribed less often than chance, p = 0.0001 consistent with epidemiological studies and multiple animal studies verifying an efficacy limiting interaction. Despite epidemiological studies indicating increased risk of accidents, alprazolam and amphetamine were prescribed more often than chance, p = 0.0001. Micromedex generated warnings for efficacy limiting interactions for five other combinations, but with no subsequent change in prescription frequency.
Neither presence of medical evidence nor warnings from Micromedex consistently affect the prescription of combinations with pharmacodynamic efficacy limiting interactions.
评估具有理论疗效限制药效学相互作用的药物联合处方的相对流行率和影响因素，这些相互作用定义为两种具有相反适应证和副作用或在作用机制的主要受体处拮抗作用的药物。
确定了 10 种药效学相互作用的 116 种组合。针对每种组合在 PubMed 上进行搜索，以评估支持临床使用或验证疗效降低的证据质量。通过搜索 Micromedex 确定是否存在降低疗效的警告。通过对 10 个参与社区心理健康中心的所有开处方者的 Genoa Healthcare 数据库进行计算机审查，确定了临床实践中的流行率。预期流行率计算为单独开每种药物的概率的乘积，并使用比例检验将其与组合的实际流行率进行比较。
八种组合的处方频率达到了 Bonferroni 校正的 p<0.001 显著性水平。其中四种是安非他命和 D2 拮抗剂的组合，每种药物的处方频率都低于预期，p<0.0001，与流行病学研究和多项动物研究一致，验证了一种疗效限制的相互作用。尽管流行病学研究表明意外事故的风险增加，但阿普唑仑和安非他命的处方频率高于预期，p<0.0001。尽管 Micromedex 针对五种其他具有药效学疗效限制相互作用的组合生成了警告，但处方频率没有随后发生变化。
医疗证据的存在或 Micromedex 的警告都不能始终如一地影响具有药效学疗效限制相互作用的组合的处方。
