Effectiveness, toxicity and safety of opioid and benzodiazepine substitutes

项目概要/摘要 2016年，美国疾病控制和预防中心（CDC）发布了“所有处方者避免 苯二氮卓类（苯并）和阿片类药物合用处方”。其他指南也建议不要使用苯类药物治疗焦虑症 因为存在更安全的替代品（降钙素-去甲肾上腺素再摄取抑制剂[SNRIs]和选择性5-羟色胺 再摄取抑制剂[SSRIs]）。自2016年CDC指南以来，使用加巴喷丁类药物作为阿片类药物替代品， 上升。虽然最近的数据显示，在CDC指南发布后，阿片类药物处方率下降， 在阿片类药物/苯并替代品处方的比率、有效性和安全性方面存在知识差距， 联合开药，特别是在药物毒性高风险人群中：残疾人、老年人 和家庭医疗保健的医疗保险登记者。我们现在建议通过以下方式来填补这一知识空白： 综合评价阿片类和苯并类替代品单独或联合应用的毒性和有效性， 与阿片类药物和苯佐类药物相比，我们预计， 药物替代和联合处方的毒性。我们的具体目标是：1。评估时间变化 类阿片、类阿片替代品、苯并类药物和苯并类替代品的处方率及其在 商业保险和医疗保险患者，以及提供者，患者，联邦和州药物政策的作用 替代和共同处方。2.检查毒性（例如，福尔斯、骨折、急诊室就诊）相关 阿片类药物和苯并类药物的替代品，以及药物替代品和 共同处方，使用纵向数据分析方法以及数据挖掘方法， 未识别的毒性。3.检查身体功能的变化以及疼痛和焦虑的措施， 医疗保险登记者处方阿片类药物和苯并类药物的替代品，以及这些结果如何随 在家庭医疗保健中，医疗保险参保者之间的药物替代和共同处方的不同组合。 我们将使用20%的国家医疗保险数据来确定老年人和残疾人医疗保险人群， Clinformatics Data Mart以识别商业保险人群。我们的总体假设是， 替代药物，无论是单独使用还是联合使用，其严重毒性发生率都比阿片类药物低得多， 苯并类，在许多临床情况下具有类似的效果。如果是这样的话，它的示范，我们的 拟议的研究应加速从类阿片和苯并类转向更安全的替代品。

Project Summary/Abstract In 2016, the Centers for Disease Control and Prevention (CDC) issued guidelines for “all prescribers to avoid co-prescribing of benzodiazepine (benzo) and opioids”. Other guidelines also advise against benzos for anxiety because safer substitutes exist (serotonin–norepinephrine reuptake inhibitors [SNRIs] and selective serotonin reuptake inhibitors [SSRIs]). Since the 2016 CDC guideline, use of gabapentinoids as an opioid substitute has risen. While recent data showed a decline in opioid prescribing rates after publication of the CDC guideline, a knowledge gap exists in terms of the rates, effectiveness and safety of opioid/benzo substitute prescribing and co-prescribing, especially in populations at high risk of drug toxicity: persons living with disabilities, the elderly and Medicare enrollees in home health care. We now propose to address this gap in knowledge by comprehensively evaluating the toxicity and effectiveness of opioid and benzo substitutes, alone or in combination, compared to opioids and benzos. We anticipate the emergence of previously unrecognized toxicities from drug substitution and co-prescribing. Our Specific Aims are: 1. Assess temporal change in prescribing rates of opioids, opioid substitutes, benzos and benzo substitutes and their co-prescribing among commercially insured and Medicare patients, and the role of provider, patient, federal and state policy on drug substitution and co-prescribing. 2. Examine toxicities (e.g., falls, fractures, emergency room visits) related to substitutes for opioids and benzos, and how toxicities vary with different combinations of drug substitution and co-prescribing, using longitudinal data analytic methods as well as data mining methods for previously unrecognized toxicities. 3. Examine changes in physical function and measures of pain and anxiety in Medicare enrollees prescribed substitutes for both opioids and benzos, and how these outcomes vary with different combinations of drug substitution and co-prescribing among Medicare enrollees in home health care. We will use 20% national Medicare data to identify the elderly and the disabled Medicare populations, and the Clinformatics Data Mart to identify commercially insured populations. Our overall hypotheses is that the substitute drugs, alone or in combination, have considerably lower rates of serious toxicity than do opioids and benzos, with similar effectiveness in many clinical situations. If this is the case, its demonstration by our proposed research should result in acceleration in the shift away from opioids and benzos to safer alternatives.