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Cochrane Database Syst Rev. 2000;(2):CD002021.

Opioid antagonists and adrenergic agonists for the management of opioid withdrawal.

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  • 1Evidence-Based Practice Unit, Drug and Alcohol Services Council, 161 Greenhill Road, Parkside, SA, Australia, 5067.

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Managed withdrawal, or detoxification, is not in itself a treatment for opioid dependence, but it is a required first step for many forms of longer-term treatment. It may also represent the end point of an extensive period of treatment such as methadone maintenance. As such, managed withdrawal is an essential component of an effective treatment system. This review is one of a series that aims to assess the evidence as to the effectiveness of approaches to managing opioid withdrawal.


To assess the effectiveness of interventions involving the combined use of opioid antagonists an adrenergic agonists to manage the acute phase of opioid withdrawal.


Multiple electronic databases, including Medline, Embase, Psychlit, Australian Medical Index and Current Contents, were searched using a strategy designed to retrieve references broadly addressing the management of opioid withdrawal. Reference lists of retrieved studies, reviews and conferences were handsearched.


Studies that were included: involved administration of an opioid antagonist in combination with an alpha2 adrenergic agonist; had modification of the signs and symptoms of withdrawal as the aim of the intervention; involved participants who had been diagnosed as primarily opioid dependent and were undergoing clinically managed withdrawal; had as their primary focus the acute phase of withdrawal; reported detail of the type and dose of drugs used and the characteristics of study participants; reported information on the nature of withdrawal symptoms experienced, the occurrence of side effects OR rates of completion of withdrawal; and were randomized or quasi-randomized controlled clinical trials or prospective controlled cohort studies comparing the combination of opioid antagonists and adrenergic antagonists with another form of treatment. (The findings of prospective single group studies or case series, and controlled studies without a comparison treatment modality were considered in the narrative component of the review without being identified as included studies).


Potentially relevant studies were assessed for inclusion by one reviewer (LRG). Inclusion decisions were confirmed by consultation between all three reviewers. Included studies were assessed by all reviewers. One reviewer (LRG) undertook data extraction with the process confirmed by consultation between all three reviewers. Three studies compared treatment using an opioid antagonist-clonidine combination with treatment using clonidine only. This review incorporates data tables comparing maximum withdrawal scores and numbers of participants completing withdrawal for these three studies.. The capacity for data analysis is limited by differences in the assessment outcomes in the three studies and the likelihood of allocation bias in one study. Consequently, meta-analysis has not been undertaken to combine the findings of the three studies.


Three studies (four reports) met the criteria for inclusi on in analytical components of this review. Six further studies were identified that managed withdrawal using opioid antagonists in combination with adrenergic agonists, but which did not meet the inclusion criteria (four were single group studies, 2 were controlled studies but did not include a comparison treatment modality). Findings of these studies are considered in narrative components of the review. Naltrexone was the primary opioid antagonist used to induce withdrawal. The most common approach was to administer naltrexone once a day, using an initial dose of 12.5mg, usually on day one or day two of treatment. Doses of clonidine were generally in the range of 01.-0.3mg three times a day. Five studies provided treatment on an outpatient basis, but all studies provided extended care on the day naltrexone was first administered. (ABSTRACT TRUNCATED)

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