Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment.
Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment.
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DOI：
10.1176/appi.ajp.2014.14081014
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发表时间：
2015-08-01
期刊：
影响因子：
--
通讯作者：
Preston KL
中科院分区：
文献类型：
--
作者：
Kowalczyk WJ;Phillips KA;Jobes ML;Kennedy AP;Ghitza UE;Agage DA;Schmittner JP;Epstein DH;Preston KL
作者测试了可乐定是否能阻止压力引起的对海洛因和可卡因的寻求。该研究还旨在通过使用患者压力的生态瞬时评估来验证关于可乐定行为作用机制的假设，从而证实药物复发大鼠模型的转化结果。作者在丁丙诺啡门诊对208名阿片类药物依赖患者进行了一项随机双盲安慰剂对照临床试验。在第5-6周期间保持戒断的118名参与者（57%）继续使用丁丙诺啡，并随机分配接受可乐定（N=61）或安慰剂（N=57）14周。每周检测三次尿液。15将停药定义为任何阿片样物质阳性或漏尿，复发定义为连续两次或两次以上的停药，停药时间和复发用考克斯回归分析，最长戒断时间用t检验，生态学瞬时评估数据用广义线性混合模型分析。在一项意向治疗分析中，可乐定在干预阶段产生了最长的阿片类药物戒断持续时间（连续天数）（34.8天[SD=3.7]与25.5天[SD=2.7]; Cohen's d=0.38）。复发时间无组间差异，但可乐定组复发时间较长（风险比=0.67，95%CI =0.45-1.00）。生态瞬时评估显示，可乐定组的日常生活压力与阿片类药物渴求部分脱钩，支持作者关于可乐定益处的假设机制。可乐定是一种容易获得的药物，在阿片类药物依赖中不仅可以减轻戒断症状，而且可以作为一种持续的维持治疗，增加戒断时间。即使在没有身体戒断的情况下，它也会减轻日常生活中渴望的压力。
The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients’ stress to test hypotheses about clonidine’s behavioral mechanism of action. The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5–6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapsesTime to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data was examined with generalized linear mixed models. In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen’s d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45–1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors’ hypothesized mechanism for clonidine’s benefits. Clonidine, a readily available medication, is useful in opioid dependence not just for alleviation of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.
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