灵活的丁丙诺啡/纳洛酮治疗模式在减少有处方类阿片使用障碍的个体中的阿片类药物使用：一项开放标签、实用、非劣效性随机对照试验。
Flexible Buprenorphine/Naloxone Model of Care for Reducing Opioid Use in Individuals With Prescription-Type Opioid Use Disorder: An Open-Label, Pragmatic, Noninferiority Randomized Controlled Trial.
机构信息
Research Centre, Centre Hospitalier de l'Université de Montréal, Montreal (Jutras-Aswad, Bruneau, Gagnon, Brissette); Department of Psychiatry and Addictology, Faculty of Medicine, Université de Montréal, Montreal (Jutras-Aswad); Department of Pharmacology and Toxicology and Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto (Le Foll); Department of Psychiatry, University of Toronto, Toronto (Le Foll, Fischer, Rehm); Dalla Lana School of Public Health, University of Toronto, Toronto (Le Foll, Rehm); Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health (CAMH), Toronto (Le Foll); Acute Care Program, CAMH, Toronto (Le Foll); British Columbia Centre on Substance Use, Vancouver (Ahamad, Wood, Fikowski, Socias); Department of Family Practice, Faculty of Medicine, University of British Columbia, Vancouver (Ahamad); Department of Family Medicine and Psychiatry, Cumming School of Medicine, University of Calgary, Alberta, Canada (Lim); Department of Family and Emergency Medicine, Faculty of Medicine, Université de Montréal, Montreal (Bruneau, Brissette); Schools of Population Health and Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand (Fischer); Centre for Applied Research in Mental Health and Addiction, Faculty of Health Science, Simon Fraser University, Vancouver (Fischer); Department of Psychiatry, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil (Fischer); Institute for Mental Health Policy Research, CAMH, Toronto (Rehm); Institute of Clinical Psychology and Psychotherapy Centre and Centre for Clinical Epidemiology and Longitudinal Studies, Technische Universität Dresden, Dresden, Germany (Rehm); Department of International Health Projects, Institute for Leadership and Health Management, I.M. Sechenov First Moscow State Medical University, Moscow (Rehm); School of Public Health, University of Alberta, Edmonton, Canada (Wild); Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver (Wood, Socias); Unité de Recherche Clinique Appliquée, Research Centre, Centre Hospitalier Universitaire Sainte-Justine, Montreal (Ledjiar, Masse); Department of Social and Preventive Medicine, School of Public Health, Université de Montréal, Montreal (Masse).
出版信息
Am J Psychiatry. 2022 Oct;179(10):726-739. doi: 10.1176/appi.ajp.21090964. Epub 2022 Jun 15.
OBJECTIVE
Extensive exposure to prescription-type opioids has resulted in major harm worldwide, calling for better-adapted approaches to opioid agonist therapy. The authors aimed to determine whether flexible take-home buprenorphine/naloxone is as effective as supervised methadone in reducing opioid use in prescription-type opioid consumers with opioid use disorder.
METHODS
This seven-site, pan-Canadian, 24-week, pragmatic, open-label, noninferiority, two-arm parallel randomized controlled trial involved treatment-seeking adults with prescription-type opioid use disorder. Participants were randomized in a 1:1 ratio to treatment with sublingual buprenorphine/naloxone (target dosage, 8 mg/2 mg to 24 mg/6 mg per day; flexible take-home dosing) or oral methadone (≈60-120 mg/day; closely supervised). The primary outcome was the proportion of opioid-free urine drug screens over 24 weeks (noninferiority margin, 15%). All randomized participants were analyzed, excluding one who died shortly after randomization, for the primary analysis (modified intention-to-treat analysis).
RESULTS
Of 272 participants recruited (mean age, 39 years [SD=11]; 34.2% female), 138 were randomized to buprenorphine/naloxone and 134 to methadone. The mean proportion of opioid-free urine drug screens was 24.0% (SD=34.4) in the buprenorphine/naloxone group and 18.5% (SD=30.5) in the methadone group, with a 5.6% adjusted mean difference (95% CI=-0.3, +∞). Participants in the buprenorphine/naloxone group had 0.47 times the odds (95% CI=0.24, 0.90) of being retained in the assigned treatment compared with those in the methadone group. Overall, 24 drug-related adverse events were reported (12 in the buprenorphine/naloxone group [N=8/138; 5.7%] and 12 in the methadone group [N=12/134; 9.0%]) and mostly included withdrawal, hypogonadism, and overdose.
CONCLUSIONS
The buprenorphine/naloxone flexible model of care was safe and noninferior to methadone in reducing opioid use among people with prescription-type opioid use disorder. This flexibility could help expand access to opioid agonist therapy and reduce harms in the context of the opioid overdose crisis.
目的
处方类阿片药物的广泛使用在全球范围内造成了严重危害，因此需要更好地采用阿片类激动剂治疗方法。作者旨在确定灵活的丁丙诺啡/纳洛酮居家使用是否与监督下的美沙酮一样有效，以减少有阿片类药物使用障碍的处方类阿片药物使用者的阿片类药物使用。
方法
这是一项在加拿大 7 个地点进行的、为期 24 周的、实用的、开放性、非劣效性、2 臂平行随机对照试验，涉及有处方类阿片药物使用障碍的寻求治疗的成年人。参与者按照 1:1 的比例随机分配接受舌下丁丙诺啡/纳洛酮（目标剂量，每天 8 毫克/2 毫克至 24 毫克/6 毫克；灵活的居家剂量）或口服美沙酮（≈60-120 毫克/天；密切监督）治疗。主要结局是 24 周内阿片类药物尿液药物筛查呈阴性的比例（非劣效性边界，15%）。对所有随机参与者（排除一名在随机分组后不久死亡的参与者）进行了主要分析（修改后的意向治疗分析）。
结果
在招募的 272 名参与者（平均年龄 39 岁[SD=11]；34.2%为女性）中，138 名被随机分配到丁丙诺啡/纳洛酮组，134 名被随机分配到美沙酮组。丁丙诺啡/纳洛酮组的阿片类药物尿液药物筛查呈阴性的平均比例为 24.0%（SD=34.4），美沙酮组为 18.5%（SD=30.5），调整后的平均差异为 5.6%（95%CI=-0.3，+∞）。与美沙酮组相比，丁丙诺啡/纳洛酮组的参与者保留在指定治疗中的可能性高 47%（95%CI=0.24，0.90）。总体而言，报告了 24 例与药物相关的不良事件（丁丙诺啡/纳洛酮组 12 例[8/138；5.7%]，美沙酮组 12 例[12/134；9.0%]），主要包括戒断、性腺功能减退和过量。
结论
丁丙诺啡/纳洛酮灵活的护理模式在减少有处方类阿片药物使用障碍的人群中的阿片类药物使用方面是安全的，且不劣于美沙酮。这种灵活性可能有助于扩大阿片类激动剂治疗的可及性，并在阿片类药物过量危机的背景下减少危害。
Zotero 插件