Amato L, Davoli M, Ferri M, Ali R
Department of Epidemiology, ASL RME, via di S.Costanza 53, Rome, Lazio, Italy.
Cochrane Database Syst Rev. 2003(2):CD003409. doi: 10.1002/14651858.CD003409.
Despite widespread use of tapered methadone for detoxification from opiate dependence, the evidence of efficacy to prevent relapse and promote lifestyle change has not been systematically evaluated.
To determine whether tapered methadone is effective to manage withdrawal from opioids.
We searched: Cochrane Controlled Trials Register (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); scan of reference list of relevant articles; personal communication; conference abstracts; Internet (NIDA, Clinical Trials.org, BMJ).
All RCT which focus on the use of tapered methadone (max 30 days) versus all other pharmacological detoxification treatments, placebo and different modalities of methadone detoxification programs for the treatment of opiate withdrawal.
One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between reviewers. Qualitative assessments of the methodology of studies were carried out using validated checklists. Where possible analysis was carried out according to the "intention to treat" principles.
20 studies were included in the review, with 1357 people randomised. Comparisons: 10 studies methadone with adrenergic agonists, 7 studies different modalities of methadone detoxification, 2 studies methadone with other opioid agonists, 1 study methadone with chlordiazepoxide, 1 with placebo. The conclusions of the 10 studies that compared methadone with adrenergic agonists showed a substantial clinical difference of the two treatments in terms of retention in treatment, degree of discomfort and detoxification success rates. The conclusions of the 6 studies that compare different methadone reduction schedules, showed that different modalities produce different responses in terms of time course of withdrawal, severity of withdrawal response and in terms of subsequent engagement with treatment. Regarding the studies that compare methadone with other opioid agonists, methadyl acetate performed similarly to methadone on most process and outcome measures, while methadone reduced severity of withdrawal and had fewer drop-outs than did a propoxyphene group. Using chlordiazepoxide vs methadone, the two drugs had similar results in terms of overall effectiveness. Comparing methadone with placebo more severe withdrawal and more drop outs founded in the placebo group. The results indicate that tapered methadone and other medications used in the included studies are effective in the treatment of the heroin withdrawal syndrome, although symptoms experienced by subjects differed according to the medication used and the program adopted. Regardless of which medication is selected for heroin detoxification, the rates of subsequent heroin abstinence are about equal. This suggests that the medications are similar in terms of overall effectiveness. Improvements were achieved when other services such as counseling and other supporting services were offered contemporaneously with detoxification.
REVIEWER'S CONCLUSIONS: Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, impairing the application of meta-analysis. Results of many outcomes could not be summarised because they were presented either in graphical form or provided only statistical tests and p-values. For most studies standard deviation for continuous variables were not provided. The studies included in this review confirm that slow tapering with temporary substitution of long acting opioids, accompanied by medical supervision and ancillary medications can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use. However this cannot be considered a goal for a detoxification as heroin dependence is a chronic, relapsing disorder and the goal of detoxification should be to remove or reduce dependence on heroin in a controlled and human fashion and not a treatment for heroin dependence.
尽管逐渐减量美沙酮广泛用于阿片类药物依赖的脱毒治疗,但预防复发和促进生活方式改变的疗效证据尚未得到系统评估。
确定逐渐减量美沙酮在管理阿片类药物戒断方面是否有效。
我们检索了:Cochrane对照试验注册库(2000年第1期)、MEDLINE(OVID 1966 - 2000年)、EMBASE(1980 - 2000年);扫描相关文章的参考文献列表;个人交流;会议摘要;互联网(美国国家药物滥用研究所、临床试验.org、英国医学杂志)。
所有聚焦于使用逐渐减量美沙酮(最长30天)与所有其他药物脱毒治疗、安慰剂以及美沙酮脱毒项目不同模式进行阿片类药物戒断治疗的随机对照试验。
一名评审员评估纳入研究并进行数据提取。纳入决策和整个过程经评审员之间协商确认。使用经过验证的清单对研究方法进行定性评估。尽可能按照“意向性分析”原则进行分析。
本综述纳入20项研究,1357人被随机分组。比较情况:10项研究比较美沙酮与肾上腺素能激动剂,7项研究比较美沙酮脱毒的不同模式,2项研究比较美沙酮与其他阿片类激动剂,1项研究比较美沙酮与氯氮卓,1项研究比较美沙酮与安慰剂。10项比较美沙酮与肾上腺素能激动剂的研究结论显示,两种治疗在治疗保留率、不适程度和脱毒成功率方面存在显著临床差异。6项比较不同美沙酮减量方案的研究结论表明,不同模式在戒断时间进程、戒断反应严重程度以及后续治疗参与度方面产生不同反应。关于比较美沙酮与其他阿片类激动剂的研究,美沙酮乙酸酯在大多数过程和结局指标上与美沙酮表现相似,而美沙酮在减轻戒断严重程度方面优于丙氧芬组且退出率更低。比较氯氮卓与美沙酮,两种药物在总体疗效方面结果相似。比较美沙酮与安慰剂,安慰剂组出现更严重的戒断反应和更多退出情况。结果表明,本综述纳入研究中使用的逐渐减量美沙酮和其他药物在治疗海洛因戒断综合征方面有效,尽管受试者经历的症状因所用药物和采用的方案而异。无论选择哪种药物进行海洛因脱毒,后续海洛因戒断率大致相同。这表明这些药物在总体疗效方面相似。当脱毒同时提供咨询和其他支持服务等其他服务时,取得了改善。
文献数据难以比较;各项目在持续时间、设计和治疗目标方面差异很大,不利于荟萃分析的应用。许多结局结果无法汇总,因为它们要么以图表形式呈现,要么仅提供统计检验和p值。大多数研究未提供连续变量的标准差。本综述纳入的研究证实,在长效阿片类药物临时替代的情况下缓慢减量,同时进行医学监督和辅助用药,可以减轻戒断严重程度。然而,大多数患者复发使用海洛因。然而,这不能被视为脱毒的目标,因为海洛因依赖是一种慢性复发性疾病,脱毒的目标应该是以可控且人道人性化的方式消除或减少对海洛因的依赖,而不是治疗海洛因依赖。