Bekhterev Research Psychoneurological Institute, St Petersburg State Pavlov Medical University, St Petersburg, Russia.
Lancet. 2011 Apr 30;377(9776):1506-13. doi: 10.1016/S0140-6736(11)60358-9.
Opioid dependence is associated with low rates of treatment-seeking, poor adherence to treatment, frequent relapse, and major societal consequences. We aimed to assess the efficacy, safety, and patient-reported outcomes of an injectable, once monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification.
We did a double-blind, placebo-controlled, randomised, 24-week trial of patients with opioid dependence disorder. Patients aged 18 years or over who had 30 days or less of inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX or placebo by an interactive voice response system, stratified by site and gender in a centralised, permuted-block method. Participants also received 12 biweekly counselling sessions. Participants, investigators, staff , and the sponsor were masked to treatment allocation. The primary endpoint was the response profile for confirmed abstinence during weeks 5–24, assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported opioid-free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00678418.
Between July 3, 2008, and Oct 5, 2009, 250 patients were randomly assigned to XR-NTX (n=126) or placebo (n=124). The median proportion of weeks of confirmed abstinence was 90·0% (95% CI 69·9–92·4) in the XR-NTX group compared with 35·0% (11·4–63·8) in the placebo group (p=0·0002). Patients in the XR-NTX group self-reported a median of 99·2% (range 89·1–99·4) opioid-free days compared with 60·4% (46·2–94·0) for the placebo group (p=0·0004). The mean change in craving was –10·1 (95% CI –12·3 to –7·8) in the XR-NTX group compared with 0·7 (–3·1 to 4·4) in the placebo group (p<0·0001). Median retention was over 168 days in the XR-NTX group compared with 96 days (95% CI 63–165) in the placebo group (p=0·0042). Naloxone challenge confirmed relapse to physiological opioid dependence in 17 patients in the placebo group compared with one in the XR-NTX group (p<0·0001). XR-NTX was well tolerated. Two patients in each group discontinued owing to adverse events. No XR-NTX-treated patients died, overdosed, or discontinued owing to severe adverse events.
XR-NTX represents a new treatment option that is distinct from opioid agonist maintenance treatment. XR-NTX in conjunction with psychosocial treatment might improve acceptance of opioid dependence pharmacotherapy and provide a useful treatment option for many patients.
Alkermes.
阿片类药物依赖与寻求治疗的比例低、治疗依从性差、频繁复发以及对社会造成重大影响有关。我们旨在评估纳曲酮（naltrexone，XR-NTX）每月一次的缓释注射制剂对接受解毒治疗的阿片类药物依赖患者的疗效、安全性和患者报告结局。
我们进行了一项双盲、安慰剂对照、随机、24 周的试验，纳入了患有阿片类药物依赖障碍的患者。年龄在 18 岁及以上、有 30 天或更短的住院解毒期和 7 天或更长时间未使用任何阿片类药物的患者在俄罗斯的 13 个临床中心入组。我们通过交互式语音应答系统，以 1:1 的比例将患者随机分配（分层因素为：中心和性别）至 XR-NTX 380mg 或安慰剂组，分组方法为中央、区组随机化。参与者还接受了 12 次双周咨询。参与者、研究者、工作人员和赞助商对治疗分配均设盲。主要终点为第 5-24 周时确认的尿药物检测和自我报告无用药的戒断反应谱，用于评估。次要终点包括自我报告的无阿片类药物天数、阿片类药物渴求评分、保留天数和复发性生理阿片类药物依赖。分析方法为意向治疗。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00678418。
2008 年 7 月 3 日至 2009 年 10 月 5 日期间，250 名患者被随机分配至 XR-NTX 组（n=126）或安慰剂组（n=124）。与安慰剂组（35.0%[11.4-63.8]）相比，XR-NTX 组的确认戒断周数中位数为 90.0%（95%CI：69.9-92.4）（p=0.0002）。与安慰剂组（60.4%[46.2-94.0]）相比，XR-NTX 组的自我报告的无阿片类药物天数中位数为 99.2%（范围：89.1-99.4）（p=0.0004）。与安慰剂组（0.7[−3.1 至 4.4]）相比，XR-NTX 组的渴求变化平均值为-10.1（95%CI：-12.3 至-7.8）（p<0.0001）。与安慰剂组（96 天[95%CI：63-165]）相比，XR-NTX 组的中位保留天数超过 168 天（p=0.0042）。纳洛酮挑战证实，安慰剂组中有 17 名患者出现复发性生理阿片类药物依赖，而 XR-NTX 组仅有 1 名患者出现复发性生理阿片类药物依赖（p<0.0001）。XR-NTX 耐受性良好。两组各有 2 名患者因不良事件而停药。无 XR-NTX 治疗的患者死亡、过量或因严重不良事件而停药。
XR-NTX 代表了一种新的治疗选择，与阿片类药物激动剂维持治疗不同。XR-NTX 联合心理社会治疗可能会提高对阿片类药物依赖药物治疗的接受度，并为许多患者提供有用的治疗选择。
Alkermes。
