Drug Interactions Involving Second-generation Antipsychotic Agents Leading to Sudden Cardiac Arrest

涉及第二代抗精神病药物的药物相互作用导致心脏骤停

• 批准号: 10501196
• 负责人: Sean Hennessy
• 金额: $ 67.99万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-06 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10501196
• 关键词: Address; Adult; Adverse Drug Experience Report; Adverse drug event; Affect; Agitation; American; Antipsychotic Agents; Arrhythmia; Bipolar Disorder; Case Study; Cessation of life; Clozapine; Controlled Study; Decision Support Systems; Dementia; Dose; Drug Combinations; Drug Interactions; Drug Kinetics; Drug usage; Etiology; Fatigue; General Population; Generations; Health; Heart Arrest; High Prevalence; Hospitals; Knowledge; Lead; Life; Life Expectancy; Longevity; Major Depressive Disorder; Mental Health; Meta-Analysis; Nature; Newsletter; Odds Ratio; Outcome; Patients; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacotherapy; Polypharmacy; Population; Population Research; Positioning Attribute; Prevalence; Psychoses; Psychotropic Drugs; Publishing; Research; Risk; Risk Factors; Safety; Sample Size; Schizophrenia; Series; Source; Study of serum; Time; Torsades de Pointes; Translating; Validation; Ventricular Arrhythmia; common treatment; computerized; evidence base; improved; medication safety; prevent; quetiapine; screening; support tools; systematic review; webinar

Schizophrenia affects approximately 1.1% of the population, or approximately 3.5 million Americans. The life expectancy of persons with schizophrenia is 10-25 years less than that of the general population, and has not improved in recent decades. Sudden cardiac arrest (SCA) and ventricular arrhythmia (VA), which account for 8-10% of all deaths in this population, is three times as common among those with than without schizophrenia. The most clearly established risk factor for SCA/VA in persons with schizophrenia is the use of antipsychotic agents, and this risk is dose-dependent. Second-generation antipsychotic agents (SGAs) are the most common treatment for schizophrenia, and are also used for other common mental health conditions including bipolar disorder, major depressive disorder, and psychosis/agitation associated with dementia. The prevalence of current antipsychotic drug use in US adults is 1.6%, or 3.8 million adults. A recent meta-analysis found that several widely used SGAs are associated with an elevated risk of SCA/VA. Given the high prevalence of polypharmacy in persons with schizophrenia and other mental health conditions, and the high potential for drug interactions in persons taking SGAs, clinicians badly need evidence-based guidance on which drugs do and do not increase the risk of SCA/VA in persons taking specific SGAs. Unfortunately, almost all available evidence about the health effects of potential DDIs involving SGAs comes from either 1) spontaneously reported adverse drug events, which provide limited evidence for causation because of their anecdotal nature, or from 2) pharmacokinetic studies of serum concentrations of SGAs, which include few subjects and do not examine health end-points. A more rigorous approach to identifying and elucidating drug interactions will help to identify drug-drug pairs that truly increase the risk of SCA/VA, and improve the safety of pharmacotherapy provided to persons with schizophrenia and other mental health conditions. To address these critical knowledge gaps about which drugs should and should not be avoided in persons receiving commonly used second generation antipsychotic drugs, we will perform high-throughput pharmacoepidemiology screening to identify drugs that may increase the rate of out-of-hospital SCA/VA in persons taking commonly used second-generation antipsychotic agents. Then, in two independent validation populations, we will conduct hypothesis- driven etiologic pharmacoepidemiology studies to either confirm or refute high-priority potential drug interactions, and elucidate factors that place patients at increased risk of out-of-hospital SCA/VA associated with specific drug pairs. The results of this research will provide drug interaction compendia editors with valid, actionable evidence that will allow them to warn clinicians about truly risky drug combinations. Of equal importance, this research will allow clinicians to be relieved of unnecessary and burdensome alerts about drug combinations that can actually be administered safely. We further propose to enhance the impact of our research by disseminating key findings through our ongoing series of webinars, newsletters, and videos that we produce for our established stakeholder group of editors and curators of drug interaction compendia and computerized decision support systems.

精神分裂症影响了大约1.1%的人口，也就是大约350万美国人。预期寿命