Lifetree Clinical Research, Salt Lake City, UT 84106, USA.
Postgrad Med. 2011 Sep;123(5):155-64. doi: 10.3810/pgm.2011.09.2471.
To determine the number of steps and identify characteristics associated with attaining a stable dose of morphine sulfate and sequestered naltrexone extended release capsules (MS-sNT).
Data from an open-label, long-term multicenter study designed to assess the safety of MS-sNT for managing chronic (≥ 3 m), moderate-to-severe pain were analyzed post hoc. Initial MS-sNT dose was 20 mg twice daily (BID) for opioid-naïve patients and 50% to 75% of current daily opioid dose for opioid-experienced patients. Dose adjustments upward/downward were allowed throughout the study with ≥ 3 days between increases; opioid-experienced patients could increase ≥ 24 hours after initial drug dispensing. Nonopioid analgesics were permitted as rescue medication. Stable dose was defined post hoc as one maintained for 2 consecutive study visits.
Overall, 69% of patients (n = 319/465) achieved a stable dose; 85% (n = 272) achieved a stable dose in ≤ 2 titration dose adjustments or "steps," and 96% (n = 305) achieved a stable dose in ≤ 4 steps. The mean time to stable dose was 28.9 days (standard deviation [SD], 34.1 days); the median was 12 days. A stable dose was achieved in 70% (118/168) of opioid-naïve patients (mean, 24.2 days [SD, 33.4 days]; median, 8 days) and 68% (201/297) of opioid-experienced patients (mean, 31.7 days [SD, 34.3 days]; median, 25 days). A stable dose was achieved by 79% (19/24) of patients who previously used morphine, 64% (27/42) who used oxycodone, 59% (47/79) who used hydrocodone, and 71% (83/117) who used multiple opioids. Baseline pain scores were similar between patients who did and did not achieve a stable dose. At the time of stable dose achievement, average, least, worst, and current pain were all decreased from baseline.
The study provides information about anticipated rates of achieving stable opioid dose in patients who received MS-sNT for up to 1 year to manage chronic, moderate-to-severe pain. Both opioid-naïve and opioid-experienced patients achieved a stable dose of MS-sNT, generally in ≤ 2 steps. Opioid experience and previous opioid use may influence ability to achieve a stable dose and number of steps required. More studies are needed on the anticipated experience of opioid titration/conversion to help physicians and patients set expectations for initiation of and conversion between opioid therapies.
确定达到硫酸吗啡和纳曲酮缓释胶囊（MS-sNT）稳定剂量的步数，并确定与达到稳定剂量相关的特征。
对一项开放性、长期多中心研究的数据进行了事后分析，该研究旨在评估 MS-sNT 管理慢性（≥3 个月）、中重度疼痛的安全性。初始 MS-sNT 剂量为：阿片类药物初治患者为每日 2 次，每次 20mg；阿片类药物治疗经验患者为当前每日阿片类药物剂量的 50%-75%。在整个研究过程中允许剂量向上/向下调整，增加剂量之间至少间隔 3 天；阿片类药物治疗经验患者可在初始药物配药后≥24 小时增加剂量。允许使用非阿片类镇痛药作为解救药物。稳定剂量定义为连续两次就诊时维持的剂量。
总体而言，69%的患者（n=319/465）达到了稳定剂量；85%（n=272）在≤2 次滴定剂量调整或“步数”内达到了稳定剂量，96%（n=305）在≤4 次步数内达到了稳定剂量。达到稳定剂量的平均时间为 28.9 天（标准差[SD]，34.1 天）；中位数为 12 天。70%（118/168）的阿片类药物初治患者（平均 24.2 天[SD，33.4 天]；中位数 8 天）和 68%（201/297）的阿片类药物治疗经验患者（平均 31.7 天[SD，34.3 天]；中位数 25 天）达到了稳定剂量。在之前使用吗啡的 24 名患者中，有 79%（19/24）达到了稳定剂量，在之前使用羟考酮的 42 名患者中，有 64%（27/42）达到了稳定剂量，在之前使用氢可酮的 79 名患者中，有 59%（47/79）达到了稳定剂量，在之前使用多种阿片类药物的 117 名患者中，有 71%（83/117）达到了稳定剂量。达到稳定剂量的患者与未达到稳定剂量的患者的基线疼痛评分相似。在达到稳定剂量时，平均、最小、最差和当前疼痛均较基线有所下降。
该研究提供了在 1 年内接受 MS-sNT 治疗管理慢性、中重度疼痛的患者达到稳定阿片类药物剂量的预期速率的信息。阿片类药物初治和治疗经验患者均达到了 MS-sNT 的稳定剂量，通常在≤2 步内。阿片类药物治疗经验和之前的阿片类药物使用可能会影响达到稳定剂量的能力和所需的步数。需要更多关于预期阿片类药物滴定/转换经验的研究，以帮助医生和患者设定开始和转换阿片类药物治疗的预期。
