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.

IF 5.2 1区医学 Q1 PSYCHIATRY

Addiction Pub Date : 2024-11-17 DOI:10.1111/add.16715

Zhenxiang Gao, T John Winhusen, Maria P Gorenflo, Ian Dorney, Udi E Ghitza, David C Kaelber, Rong Xu

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Abstract

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.

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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。

背景和目的：苯丙胺类兴奋剂是全球使用量第二大的非法药物，但目前尚无美国食品和药物管理局（FDA）批准的治疗苯丙胺类兴奋剂使用障碍（ATSUD）的药物。本研究旨在利用一个药物发现框架，该框架整合了基于人工智能（AI）的药物预测、临床确证和作用机理分析，以确定可重新用于治疗ATSUD的FDA批准药物：首先利用基于人工智能的知识图谱模型对 FDA 批准的药物治疗 ATSUD 的潜在疗效进行优先排序。在排名前 10 位的候选药物中，氯胺酮是一种新型候选药物，很少有研究探讨其对 ATSUD 的疗效。因此，我们利用美国电子健康记录（EHR）数据开展了一项回顾性队列研究，以评估氯胺酮与 ATSUD 缓解之间的关联。最后，我们分析了氯胺酮对 ATSUD 的潜在作用机制：2019年1月至2022年6月期间接受麻醉（n = 3663）或被诊断为抑郁症（n = 4328）的ATSUD患者。结果测量是在药物处方后一年内诊断出 ATSUD 缓解：与其他麻醉药相比，氯胺酮用于 ATSUD 患者的麻醉与 ATSUD 缓解率更相关：危险比 (HR) = 1.58，95% 置信区间 (CI) = 1.15-2.17。在将氯胺酮与抗抑郁药和安非他酮/米氮平进行比较时，抑郁症 ATSUD 患者也发现了类似的结果，HR 分别为 1.51（95% CI = 1.14-2.01）和 1.68（95% CI = 1.18-2.38）。功能分析结果表明，氯胺酮靶向了几种与ATSUD相关的通路，包括神经活性配体-受体相互作用和苯丙胺成瘾：结论：临床医生开具氯胺酮处方与苯丙胺类兴奋剂使用障碍患者较高的缓解率之间似乎存在关联。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Addiction 医学-精神病学

CiteScore

10.80

自引率

6.70%

发文量

319

审稿时长

3 months

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.