Christine Paul J, Blum Joshua, Tillman Alexandra R, Braun Hannan M, Hinrichs Martin, Hurley Hermione, Al-Tayyib Alia
Department of General Internal Medicine, Denver Health and Hospital Authority, Denver, Colorado.
Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora.
JAMA Netw Open. 2025 Aug 1;8(8):e2529393. doi: 10.1001/jamanetworkopen.2025.29393.
In opioid treatment programs (OTPs), restarting methadone after missed doses is common. Current guidelines recommend significant dose decreases but do not account for maintained tolerance.
To evaluate the safety and treatment retention associated with a novel methadone restart protocol.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included participants in a public, safety-net OTP in Colorado, comparing cohorts before (2021) and after (2023) a 2022 protocol change. Eligible participants were patients who restarted methadone after 4 or more missed dosing days. Data were analyzed August 2024 through June 2025.
Restart protocol incorporating patient-reported nonprescribed opioid use and individualized assessments to determine restart doses.
Protocol implementation was measured by change in dose before vs after restart, comparing preimplementation and postimplementation periods. Primary outcome was patient safety, measured by emergency department (ED) visits within 7 days of restart (all-cause, opioid withdrawal, and overdose-related) and 7-day and 90-day all-cause mortality. The secondary outcome was 90-day treatment retention. Generalized estimating equations were used to calculate adjusted risk ratios (aRRs) comparing preimplementation and postimplementation periods, controlling for demographics and comorbid substance use. Patient and clinician satisfaction and perceived safety were surveyed.
A total of 786 patients were included in the preimplementation cohort and 780 in the postimplementation cohort; 202 patients had methadone restarts before implementation (464 restart episodes; 124 male [61.4%]; 148 ages 25 to 44 years [73.3%]; 10 Black [5.0%], 72 Hispanic [35.6%], 112 White [55.4%]) and 195 patients after implementation (489 restart episodes; 116 male [59.5%]; 123 ages 25 to 44 years [63.1%]; 12 Black [6.2%], 60 Hispanic [30.8%], 114 White [58.5%]). Most patients were insured by Medicaid (preimplementation, 164 of 202 patients [81.2%]; postimplementation, 154 of 195 patients [79.0%]). In the preimplementation period, restart doses were 32.8% lower (95% CI, 30.8%-34.7%) than the last dose prior to restart. After protocol implementation, restart doses were 3.4% lower (95% CI, 1.5%-5.3%) than the last received dose. In the preimplementation period, 44 of 464 restarts (9.5%) were followed by ED visits within 7 days, compared with 30 of 489 restarts (6.1%) in the postimplementation period (aRR, 0.61; 95% CI, 0.37-0.98). There were 4 restarts followed by death within 90 days in both the preimplementation and postimplementation periods. Treatment retention was similar in preimplementation and postimplementation periods (aRR, 0.88; 95% CI, 0.73-1.05). Survey responses indicated high acceptance and satisfaction with the protocol.
In this cohort study of individuals with opioid use disorder restarting methadone after a gap in treatment, an individualized methadone restart protocol that considered interim opioid tolerance was associated with higher restart doses without compromising safety or treatment retention. Further research is needed to evaluate if this approach improves treatment outcomes.
在阿片类药物治疗项目（OTP）中，错过剂量后重新开始使用美沙酮的情况很常见。当前指南建议大幅降低剂量，但未考虑维持的耐受性。
评估一种新型美沙酮重新开始方案的安全性和治疗持续性。
设计、地点和参与者：这项队列研究纳入了科罗拉多州一个公共安全网OTP的参与者，比较了2022年方案变更前后（2021年和2023年）的队列。符合条件的参与者是在错过4个或更多给药日后重新开始使用美沙酮的患者。数据于2024年8月至2025年6月进行分析。
重新开始方案纳入了患者报告的非处方阿片类药物使用情况和个体化评估，以确定重新开始的剂量。
通过比较实施前和实施后时期重新开始前与后的剂量变化来衡量方案的实施情况。主要结局是患者安全性，通过重新开始后7天内的急诊科（ED）就诊情况（全因、阿片类药物戒断和过量相关）以及7天和90天全因死亡率来衡量。次要结局是90天治疗持续性。使用广义估计方程计算比较实施前和实施后时期的调整风险比（aRR），控制人口统计学和合并物质使用情况。对患者和临床医生的满意度以及感知安全性进行了调查。
实施前队列共纳入786例患者，实施后队列纳入780例患者；202例患者在实施前重新开始使用美沙酮（464次重新开始事件；男性124例[61.4%]；年龄25至44岁148例[73.3%]；黑人10例[5.0%]，西班牙裔72例[35.6%]，白人112例[55.4%]），实施后195例患者（489次重新开始事件；男性116例[59.5%]；年龄25至44岁123例[63.1%]；黑人12例[6.2%]，西班牙裔60例[30.8%]，白人114例[58.5%]）。大多数患者由医疗补助保险（实施前，202例患者中的164例[81.2%]；实施后，195例患者中的154例[79.0%]）。在实施前时期，重新开始剂量比重新开始前的最后剂量低32.8%（95%CI，30.8%-34.7%）。方案实施后，重新开始剂量比最后一次接受的剂量低3.4%（95%CI，1.5%-5.3%）。在实施前时期，464次重新开始中有44次（9.5%）在7天内随后进行了ED就诊，而在实施后时期，489次重新开始中有30次（6.1%）（aRR，0.61；95%CI，0.37-0.98）。在实施前和实施后时期，均有4次重新开始后在90天内死亡。实施前和实施后时期的治疗持续性相似（aRR，0.88；95%CI，0.73-1.05）。调查回复表明对该方案的接受度和满意度较高。
在这项针对阿片类药物使用障碍患者在治疗中断后重新开始使用美沙酮的队列研究中，一种考虑了期间阿片类药物耐受性的个体化美沙酮重新开始方案与更高的重新开始剂量相关，且不影响安全性或治疗持续性。需要进一步研究以评估这种方法是否能改善治疗结局。
