Gowing L, Farrell M, Ali R, White J
Evidence-Based Practice Unit, Drug and Alcohol Services Council, 161 Greenhill Road, Parkside, SA, Australia, 5063.
Cochrane Database Syst Rev. 2001(1):CD002024. doi: 10.1002/14651858.CD002024.
Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system.
To assess the effectiveness of interventions involving the use of alpha2 adrenergic agonists (clonidine, lofexidine, guanfacine, guanabenz acetate) to manage the acute phase of opioid withdrawal.
Multiple electronic databases were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched and relevant pharmaceutical companies contacted.
Randomised or quasi-randomised controlled trials that compared alpha2 adrenergic agonists with another form of treatment (or placebo) to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent.
One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all four reviewers.
Twenty-four studies, involving 1956 participants, were included. Nineteen were randomised controlled trials; in two allocation was by participant choice, one used alternate allocation and in two the method of allocation was unclear. Ten studies compared a treatment regime based on an alpha2 adrenergic agonist with one based on reducing doses of methadone. Diversity in study design, assessment and reporting of outcomes limited the extent of quantitative analysis. From the comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone, withdrawal intensity is similar to, or marginally greater with alpha2 adrenergic agonists, but signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. The likelihood of completing withdrawal is similar, or slightly less, with clonidine or lofexidine. Clonidine is associated with more adverse effects (low blood pressure, dizziness, dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine.
REVIEWER'S CONCLUSIONS: Treatment regimes based on the alpha2 adrenergic agonists clonidine and lofexidine, and those based on reducing doses of methadone over a period of around 10 days, have similar efficacy in the management of withdrawal from heroin or methadone. Participants stay in treatment longer with methadone regimes and experience less adverse effects. The lower incidence of hypotension makes lofexidine more suited to use in outpatient settings than lofexidine. There are insufficient data available to support a conclusion on the efficacy of guanfacine.
在进行无药物治疗之前，戒毒（脱毒）是必要的。它也可能是长期治疗（如美沙酮维持治疗）的终点。有效的戒毒治疗对于一个有效的治疗系统至关重要。
评估使用α2肾上腺素能激动剂（可乐定、洛非西定、胍法辛、胍那苄醋酸盐）来管理阿片类药物戒断急性期的干预措施的有效性。
系统检索了多个电子数据库。对检索到的研究、综述和会议摘要的参考文献列表进行了手工检索，并联系了相关制药公司。
随机或半随机对照试验，比较α2肾上腺素能激动剂与另一种治疗形式（或安慰剂），以改善主要依赖阿片类药物的参与者的戒断体征和症状。
一名评审员评估研究是否纳入并进行数据提取。所有四名评审员之间的协商确认了纳入决定和整个过程。
纳入了24项研究，涉及1956名参与者。19项为随机对照试验；两项是由参与者选择分配方式，一项采用交替分配，两项分配方法不明确。10项研究比较了基于α2肾上腺素能激动剂的治疗方案与基于逐渐减少美沙酮剂量的治疗方案。研究设计、结果评估和报告的多样性限制了定量分析的范围。从α2肾上腺素能激动剂方案与逐渐减少美沙酮剂量方案的比较来看，戒断强度与α2肾上腺素能激动剂相似，或略高，但戒断体征和症状在治疗中出现和缓解得更早。使用美沙酮治疗的参与者在治疗中停留的时间更长。使用可乐定或洛非西定完成戒断的可能性相似，或略低。与逐渐减少美沙酮剂量相比，可乐定与更多的不良反应（低血压、头晕、口干、乏力）相关。洛非西定降低血压的程度不如可乐定，但在其他方面与可乐定相似。
基于α2肾上腺素能激动剂可乐定和洛非西定的治疗方案，以及在大约10天内逐渐减少美沙酮剂量的治疗方案，在管理海洛因或美沙酮戒断方面具有相似的疗效。使用美沙酮治疗方案的参与者在治疗中停留的时间更长，且不良反应更少。低血压发生率较低使得洛非西定比可乐定更适合在门诊环境中使用。没有足够的数据支持关于胍法辛疗效的结论。
