Opioid antagonists with minimal sedation for opioid withdrawal

Abstract

Background: Managed withdrawal is necessary prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment.

Objectives: To assess the effectiveness of opioid antagonists in combination with minimal sedation to induce withdrawal, in terms of intensity of withdrawal, adverse effects and completion of treatment.

Search strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2005, which includes the Cochrane Drugs and Alcohol Group register), MEDLINE (January 1966 to August 2005), EMBASE (January 1985 to August 2005), PsycINFO (1967 to August 2005), and CINAHL (1982 to July 2005) and reference lists of articles.

Selection criteria: Experimental interventions involved 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 regime.

Data collection and analysis: One reviewer assessed studies for inclusion and undertook data extraction and trial quality. Study authors were contacted for additional information.

Main results: Nine studies (5 randomised controlled trials), involving 775 participants, met the inclusion criteria for the review. Withdrawal induced by opioid antagonists in combination with an adrenergic agonist is more intense than withdrawal managed with clonidine or lofexidine alone, but the overall severity is less. Limited data showed that antagonist-induced withdrawal may be more severe when the last opioid used was methadone rather than heroin or another short-acting opioid. Delirium may occur following the first dose of opioid antagonist, particularly with higher doses (> 25mg naltrexone). The studies included suggest there is no significant difference in rates of completion of treatment for withdrawal induced by opioid antagonists, in combination with an adrenergic agonist, compared with adrenergic agonist alone.

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.