Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Drug Alcohol Depend. 2022 Oct 1;239:109609. doi: 10.1016/j.drugalcdep.2022.109609. Epub 2022 Aug 30.
Although there is consensus that having a "high-enough" dose of buprenorphine (BUP-NX) or methadone is important for reducing relapse to opioid use, there is debate about what this dose is and how it should be attained. We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone.
This was a secondary analysis of three comparative effectiveness trials. We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the "hybrid strategy"), and 4) keeping dose constant after the first 2 weeks of treatment. We used a longitudinal sequentially doubly robust estimator to estimate contrasts between dosing strategies on risk of relapse.
For BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse. For methadone, holding dose constant resulted in greatest risk of relapse; the other three strategies performed similarly. For example, the hybrid strategy reduced week 12 relapse risk by 13 % (RR: 0.87, 95 %CI: 0.83-0.95) and by 20 % (RR: 0.80, 95 %CI: 0.71-0.90) for BUP-NX and methadone respectively, as compared to holding dose constant.
Doses should be targeted toward minimum thresholds and, in the case of BUP-NX, raised when patients continue to use opioids.
虽然人们普遍认为，给予足够高剂量的丁丙诺啡（BUP-NX）或美沙酮对于减少阿片类药物使用的复发至关重要，但对于这个剂量是多少以及应该如何达到这个剂量，仍存在争议。我们分别评估了 BUP-NX 和美沙酮治疗 12 周期间，不同剂量策略对复发风险的影响程度。
这是三项比较有效性试验的二次分析。我们检查了四种剂量策略：1）根据患者特定的阿片类药物使用情况增加剂量；2）每周增加剂量，直到达到某个最低剂量（16mg BUP，100mg 美沙酮）；3）每周增加剂量，直到达到某个最低剂量，此后根据阿片类药物使用情况增加剂量（称为“混合策略”）；4）在治疗的前 2 周后保持剂量不变。我们使用纵向顺序双稳健估计量来估计不同剂量策略对复发风险的差异。
对于 BUP-NX，采用混合策略增加剂量可降低复发风险。对于美沙酮，保持剂量不变会导致最大的复发风险；其他三种策略的表现相似。例如，与保持剂量不变相比，混合策略可分别降低 BUP-NX 和美沙酮第 12 周的复发风险 13%（RR：0.87，95%CI：0.83-0.95）和 20%（RR：0.80，95%CI：0.71-0.90）。
剂量应针对最低阈值，并且在 BUP-NX 的情况下，当患者继续使用阿片类药物时，应提高剂量。
