It is feasible to use opioid antagonists with minimal sedation to manage opioid withdrawal but the value of the approach is uncertain.

Gowing L, Ali R, White JM

Published Online:

October 7, 2009

Opioid antagonists induce withdrawal by displacing opioids from their receptors. Adrenergic agonists, acting through non-opioid mechanisms, can reduce withdrawal symptoms induced by antagonists. The use of these substances in combination is a feasible approach to the management of opioid withdrawal, but evidence on the effectiveness of the approach is of low quality leaving uncertainty about its value.

Abstract (click to read)

Background:

Managed withdrawal is a necessary step prior to drug-free treatment or as the end point of long-term substitution treatment.

Objectives:

To assess the effectiveness of opioid antagonists in combination with minimal sedation to manage opioid withdrawal.

Search strategy:

We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2008), MEDLINE (January 1966-July 2008), EMBASE (January 1985-2008 Week 31), PsycINFO (1967 to 7 August 2008) and reference lists of articles.

Selection criteria:

Controlled studies of interventions involving the use of opioid antagonists in combination with minimal sedation to manage withdrawal in opioid-dependent participants compared with other approaches or different opioid antagonist regimes.

Data collection and analysis:

One author assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all authors.

Main results:

Nine studies (6 randomised controlled trials), involving 837 participants, met the inclusion criteria for the review.

The quality of the evidence is low, but suggests that withdrawal induced by opioid antagonists in combination with an adrenergic agonist is more intense than withdrawal managed with clonidine or lofexidine alone, while the overall severity is less. Delirium may occur following the first dose of opioid antagonist, particularly with higher doses (> 25mg naltrexone).

In some situations antagonist-induced withdrawal may be associated with significantly higher rates of completion of treatment, comp[ared to withdrawal managed primarily with adrenergic agonists. However, this outcome has not been produced consistently, and the extent of any benefit is highly uncertain.

Authors' conclusions:

The use of opioid antagonists combined with alpha2-adrenergic agonists is a feasible approach to the management of opioid withdrawal. However, it is unclear whether this approach reduces the duration of withdrawal or facilitates transfer to naltrexone treatment to a greater extent than withdrawal managed primarily with an adrenergic agonist.

A high level of monitoring and support is desirable for several hours following administration of opioid antagonists because of the possibility of vomiting, diarrhoea and delirium.

Further research is required to confirm the relative effectiveness of antagonist-induced regimes, as well as variables influencing the severity of withdrawal, adverse effects, the most effective antagonist-based treatment regime, and approaches that might increase retention in subsequent naltrexone maintenance treatment.

This record should be cited as:

Gowing L, Ali R, White JM. Opioid antagonists with minimal sedation for opioid withdrawal. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD002021. DOI: 10.1002/14651858.CD002021.pub3

Assessed as up to date:

January 15, 2009

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Primary Review Group:

Drugs and Alcohol Group

Health topics:

Tobacco, drugs, & alcohol dependence > Opioids, opiates, heroin > Dextoxification

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

It is feasible to use opioid antagonists with minimal sedation to manage opioid withdrawal but the value of the approach is uncertain.

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