注射用纳曲酮微球预防阿片类药物依赖复吸的临床研究

Clinical study of naltrexone microspheres for injection on preventing relapse effect from opioid dependence

目的：评估注射纳曲酮微球预防阿片类药物依赖复吸的疗效和安全性。方法：筛选符合海洛因依赖且无其他躯体疾病，年龄18~45岁，至少有3次复吸史，自愿接受戒毒治疗的患者24例。随机纳入研究组及对照组，研究组注射纳曲酮微球，对照组服用盐酸纳曲酮片；疗程均为20周，停药后随访4周。在第0、2、4、8、12、16、20、24周时观察疗效和安全性。结果：研究组和对照组各纳入12名海洛因依赖患者，1名患者未参加随访，2名患者中途退出，共有21名患者（研究组11人，对照组10人）顺利完成实验。自给药后4~24周，研究组尿检阴性率均高于对照组，其差异在接受治疗后8周时有统计学意义（P =0.035）。研究组5人（45.5%）及对照组中2人（20.0%）完成全部访视。研究组与对照组的平均脱落时间分别为18.55周与11.40周，差异有统计学意义（P=0.033）。自用药后4周，研究组用药1 h后渴求评分均低于对照组，在访视5（用药后4周）和访视7（用药后12周）时有显著性差异（P=0.028；P=0.042）。在整个研究过程中，没有出现严重的治疗相关不良事件。结论：与口服纳曲酮片相比，注射用纳曲酮微球能降低患者复吸风险，减轻患者戒毒期间对毒品的渴求程度，提高患者服药依从性，增加其自愿接受治疗的时间，无不良事件发生风险，可以考虑作为海洛因依赖防复吸治疗的有效手段。

Objective：To evaluate the efifcacy and safety of naltrexone microspheres for injection on preventing relapse from opioid dependence. Methods：There were 24 participants collected in our study, who were heroin dependent patients （diagnosed by DSM-Ⅳ） without physical conditions between the age of 18 and 45 years with at least three times relapse and were voluntary for treatment. All the subjects were randomly divided into experimental group and control group. The participants in experimental group were administered naltrexone microspheres for injection once every four weeks, totally 5 doses, while participants in control group were dosed oral naltrexone daily for 20 weeks. A 4-week follow-up was performed after medication cessation. Efifcacy and safety were evaluated at 0, 2, 4, 8, 12, 16, 20, 24 weeks. Results： Each group was enrolled 12 heroin dependent patients. One subject did not show in any follow-up and two subjects violated study protocol at visit 3 （the initiation of medication）. There were total twenty-one subjects （experimental group, n=11;control group, n=l0） successfully completed in this study. In 4-24 weeks after administration, the negative percentage of urine samples of naltrexone microspheres for injection group were higher than that of control group and there was signiifcant difference between the control and experimental group at 8th week. There were ifve subjects （45.5%） in the experimental group ifnished the whole study, while two subjects （20.0%） in the control group completed this trial. The average time for dropout in experimental group was 18.55 weeks which was signiifcantly longer than that of control group, 11.40 weeks （P=0.033）. Since 4 weeks after administration, the craving scores after one hour with administration in experimental group were substantially less than those of control group, which showed signiifcant differences at visit 5 （P=0.028） and visit 7 （P=0.042）. Through the whole study, no serious treatment-related adverse events occurred. Conclusion：Compared with oral naltrexone, this study indicated that naltrexone microspheres for injection could decrease the relapse risk of heroin dependents, lessen their craving during abstinence, elevate their compliance and increase the time of voluntary therapy without increasing the risk of adverse events.