Zhenxiang Gao, T John Winhusen, Maria P Gorenflo, Ian Dorney, Udi E Ghitza, David C Kaelber, Rong Xu
{"title":"基于人工智能的药物再利用与电子健康记录临床确证：氯胺酮作为苯丙胺类兴奋剂使用障碍潜在治疗方法的案例。","authors":"Zhenxiang Gao, T John Winhusen, Maria P Gorenflo, Ian Dorney, Udi E Ghitza, David C Kaelber, Rong Xu","doi":"10.1111/add.16715","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and aims: </strong>Amphetamine-type stimulants are the second-most used illicit drugs globally, yet there are no US Food and Drug Administration (FDA)-approved treatments for amphetamine-type stimulant use disorders (ATSUD). The aim of this study was to utilize a drug discovery framework that integrates artificial intelligence (AI)-based drug prediction, clinical corroboration and mechanism of action analysis to identify FDA-approved drugs that can be repurposed for treating ATSUD.</p><p><strong>Design and setting: </strong>An AI-based knowledge graph model was first utilized to prioritize FDA-approved drugs in their potential efficacy for treating ATSUD. Among the top 10 ranked candidate drugs, ketamine represented a novel candidate with few studies examining its effects on ATSUD. We therefore conducted a retrospective cohort study to assess the association between ketamine and ATSUD remission using US electronic health record (EHR) data. Finally, we analyzed the potential mechanisms of action of ketamine in the context of ATSUD.</p><p><strong>Participants and measurements: </strong>ATSUD patients who received anesthesia (n = 3663) or were diagnosed with depression (n = 4328) between January 2019 and June 2022. The outcome measure was the diagnosis of ATSUD remission within one year of the drug prescription.</p><p><strong>Findings: </strong>Ketamine for anesthesia in ATSUD patients was associated with greater ATSUD remission compared with other anesthetics: hazard ratio (HR) = 1.58, 95% confidence interval (CI) = 1.15-2.17. Similar results were found for ATSUD patients with depression when comparing ketamine with antidepressants and bupropion/mirtazapine with HRs of 1.51 (95% CI = 1.14-2.01) and 1.68 (95% CI = 1.18-2.38), respectively. Functional analyses demonstrated that ketamine targets several ATSUD-associated pathways including neuroactive ligand-receptor interaction and amphetamine addiction.</p><p><strong>Conclusions: </strong>There appears to be an association between clinician-prescribed ketamine and higher remission rates in patients with amphetamine-type stimulant use disorders.</p>","PeriodicalId":109,"journal":{"name":"Addiction","volume":" ","pages":""},"PeriodicalIF":5.2000,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Artificial intelligence-based drug repurposing with electronic health record clinical corroboration: A case for ketamine as a potential treatment for amphetamine-type stimulant use disorder.\",\"authors\":\"Zhenxiang Gao, T John Winhusen, Maria P Gorenflo, Ian Dorney, Udi E Ghitza, David C Kaelber, Rong Xu\",\"doi\":\"10.1111/add.16715\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and aims: </strong>Amphetamine-type stimulants are the second-most used illicit drugs globally, yet there are no US Food and Drug Administration (FDA)-approved treatments for amphetamine-type stimulant use disorders (ATSUD). The aim of this study was to utilize a drug discovery framework that integrates artificial intelligence (AI)-based drug prediction, clinical corroboration and mechanism of action analysis to identify FDA-approved drugs that can be repurposed for treating ATSUD.</p><p><strong>Design and setting: </strong>An AI-based knowledge graph model was first utilized to prioritize FDA-approved drugs in their potential efficacy for treating ATSUD. Among the top 10 ranked candidate drugs, ketamine represented a novel candidate with few studies examining its effects on ATSUD. We therefore conducted a retrospective cohort study to assess the association between ketamine and ATSUD remission using US electronic health record (EHR) data. Finally, we analyzed the potential mechanisms of action of ketamine in the context of ATSUD.</p><p><strong>Participants and measurements: </strong>ATSUD patients who received anesthesia (n = 3663) or were diagnosed with depression (n = 4328) between January 2019 and June 2022. The outcome measure was the diagnosis of ATSUD remission within one year of the drug prescription.</p><p><strong>Findings: </strong>Ketamine for anesthesia in ATSUD patients was associated with greater ATSUD remission compared with other anesthetics: hazard ratio (HR) = 1.58, 95% confidence interval (CI) = 1.15-2.17. Similar results were found for ATSUD patients with depression when comparing ketamine with antidepressants and bupropion/mirtazapine with HRs of 1.51 (95% CI = 1.14-2.01) and 1.68 (95% CI = 1.18-2.38), respectively. Functional analyses demonstrated that ketamine targets several ATSUD-associated pathways including neuroactive ligand-receptor interaction and amphetamine addiction.</p><p><strong>Conclusions: </strong>There appears to be an association between clinician-prescribed ketamine and higher remission rates in patients with amphetamine-type stimulant use disorders.</p>\",\"PeriodicalId\":109,\"journal\":{\"name\":\"Addiction\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-11-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Addiction\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/add.16715\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Addiction","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/add.16715","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Artificial intelligence-based drug repurposing with electronic health record clinical corroboration: A case for ketamine as a potential treatment for amphetamine-type stimulant use disorder.
Background and aims: Amphetamine-type stimulants are the second-most used illicit drugs globally, yet there are no US Food and Drug Administration (FDA)-approved treatments for amphetamine-type stimulant use disorders (ATSUD). The aim of this study was to utilize a drug discovery framework that integrates artificial intelligence (AI)-based drug prediction, clinical corroboration and mechanism of action analysis to identify FDA-approved drugs that can be repurposed for treating ATSUD.
Design and setting: An AI-based knowledge graph model was first utilized to prioritize FDA-approved drugs in their potential efficacy for treating ATSUD. Among the top 10 ranked candidate drugs, ketamine represented a novel candidate with few studies examining its effects on ATSUD. We therefore conducted a retrospective cohort study to assess the association between ketamine and ATSUD remission using US electronic health record (EHR) data. Finally, we analyzed the potential mechanisms of action of ketamine in the context of ATSUD.
Participants and measurements: ATSUD patients who received anesthesia (n = 3663) or were diagnosed with depression (n = 4328) between January 2019 and June 2022. The outcome measure was the diagnosis of ATSUD remission within one year of the drug prescription.
Findings: Ketamine for anesthesia in ATSUD patients was associated with greater ATSUD remission compared with other anesthetics: hazard ratio (HR) = 1.58, 95% confidence interval (CI) = 1.15-2.17. Similar results were found for ATSUD patients with depression when comparing ketamine with antidepressants and bupropion/mirtazapine with HRs of 1.51 (95% CI = 1.14-2.01) and 1.68 (95% CI = 1.18-2.38), respectively. Functional analyses demonstrated that ketamine targets several ATSUD-associated pathways including neuroactive ligand-receptor interaction and amphetamine addiction.
Conclusions: There appears to be an association between clinician-prescribed ketamine and higher remission rates in patients with amphetamine-type stimulant use disorders.
期刊介绍：
Addiction publishes peer-reviewed research reports on pharmacological and behavioural addictions, bringing together research conducted within many different disciplines.
Its goal is to serve international and interdisciplinary scientific and clinical communication, to strengthen links between science and policy, and to stimulate and enhance the quality of debate. We seek submissions that are not only technically competent but are also original and contain information or ideas of fresh interest to our international readership. We seek to serve low- and middle-income (LAMI) countries as well as more economically developed countries.
Addiction’s scope spans human experimental, epidemiological, social science, historical, clinical and policy research relating to addiction, primarily but not exclusively in the areas of psychoactive substance use and/or gambling. In addition to original research, the journal features editorials, commentaries, reviews, letters, and book reviews.
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