Effectiveness, toxicity and safety of opioid and benzodiazepine substitutes

项目摘要/摘要 2016年，疾病控制和预防中心(CDC)发布了指导方针，要求所有处方者避免 苯二氮卓(苯并)和阿片类药物的联合处方“。其他指南也建议人们不要服用苯并酚来缓解焦虑。 因为存在更安全的替代品(5-羟色胺-去甲肾上腺素再摄取抑制剂[SNRI]和选择性5-羟色胺 重摄取抑制剂[SSRIs])。自2016年疾控中心指南以来，使用加巴喷丁作为阿片类药物替代品 复活了。虽然最近的数据显示，在疾控中心指南发布后，阿片类药物处方率下降，但 在阿片/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 联合处方，特别是在药物中毒高危人群中：残疾人、老年人 以及参加家庭医疗保健的联邦医疗保险参与者。我们现在建议通过以下方式解决这一知识差距 综合评价阿片类药物和苯并代用品的毒性和有效性 与阿片类药物和苯并类药物相比。我们预计会出现以前未被认识到的 药物替代和联合处方的毒性。我们的具体目标是：1.评估 阿片类药物、阿片类代用品、苯并物和苯并代用品的处方比率及其联合处方 商业保险和医疗保险患者，以及药物提供者、患者、联邦和州政策的作用 替代和联合处方。2.检查与以下各项有关的毒性(如跌倒、骨折、急诊室就诊) 阿片类药物和苯并类药物的替代品，以及不同药物替代和不同组合的毒性如何变化 联合处方，使用纵向数据分析方法以及以前的数据挖掘方法 无法识别的毒物。3.检查身体机能的变化以及疼痛和焦虑的测量 医疗保险参保人开出阿片类药物和苯并类药物的替代品，以及这些结果如何随 在家庭保健中，联邦医疗保险参与者之间的药物替代和联合处方的不同组合。 我们将使用20%的全国医疗保险数据来识别老年和残疾人医疗保险人口，以及 Clinformatics Data Mart用于识别商业保险人群。我们的总体假设是 替代药物，单独或联合使用，严重毒性的比率比阿片类药物和 苯并，在许多临床情况下都有类似的效果。如果是这样的话，我们的 拟议的研究应加速从阿片类药物和苯并类药物向更安全的替代品的转变。

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.