Kowalczyk William J, Phillips Karran A, Jobes Michelle L, Kennedy Ashley P, Ghitza Udi E, Agage Daniel A, Schmittner John P, Epstein David H, Preston Kenzie L
From the Clinical Pharmacology and Therapeutics Research Branch, NIDA, Baltimore; the Clinical Trials Operations and Biostatistics Branch, NIMH, Rockville, Md.; the Center for Clinical Trials Network, NIDA, Bethesda, Md.; and Advanced Heart Failure Program, Spectrum Health System, Grand Rapids, Mich.
Am J Psychiatry. 2015 Aug 1;172(8):760-7. doi: 10.1176/appi.ajp.2014.14081014. Epub 2015 Mar 17.
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 lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were 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 reduction 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.
作者测试可乐定是否能阻断应激诱导的海洛因和可卡因觅求行为。该研究还旨在通过对患者应激进行生态瞬时评估以检验关于可乐定行为作用机制的假设，从而确认来自药物复发大鼠模型的转化研究结果。
作者在一家门诊丁丙诺啡诊所对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周保持禁欲的118名参与者（57%）继续服用丁丙诺啡，并被随机分配接受可乐定（N = 61）或安慰剂（N = 57）治疗14周。每周对尿液进行三次检测。失误被定义为任何阿片类药物阳性或错过尿液检测，复发被定义为连续两次或更多次失误。通过Cox回归分析失误和复发时间；用t检验分析最长禁欲期，用广义线性混合模型分析生态瞬时评估数据。
在意向性分析中，可乐定在干预阶段产生了最长的阿片类药物禁欲持续时间（连续天数）（34.8天[标准差 = 3.7]，而安慰剂组为25.5天[标准差 = 2.7]；Cohen's d = 0.38）。复发时间上两组无差异，但可乐定组出现失误的时间更长（风险比 = 0.67，95%置信区间 = 0.45 - 1.00）。生态瞬时评估表明，可乐定组日常生活应激与阿片类药物渴求部分脱钩，支持了作者关于可乐定益处的假设机制。
可乐定作为一种 readily available medication，不仅对减少戒断症状有用，而且作为辅助维持治疗可增加禁欲持续时间，对阿片类药物依赖有效。即使在没有身体戒断的情况下，它也能在日常生活中使应激与渴求脱钩。 （注：原文“readily available medication”直译为“现成可用的药物”，但在医学语境中不太符合习惯表述，可结合上下文灵活调整，这里暂保留原文表述。）
