Opioid antagonists with minimal sedation for opioid withdrawal

Managed withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance.

To assess the effectiveness of interventions involving opioid antagonists to induce withdrawal, in combination with medication to ameliorate symptoms but with minimal sedation.

Multiple databases were searched using a strategy designed to retrieve references broadly addressing opioid withdrawal. Reference lists of retrieved studies, reviews and conference abstracts were handsearched.

Randomised or quasi-randomised controlled clinical trials or prospective controlled cohort studies that compared antagonist-induced (conscious) withdrawal with other approaches to modify the signs and symptoms of withdrawal in opioid-dependent participants.

One reviewer assessed potentially relevant studies for inclusion and undertook data extraction. All inclusion decisions and the overall process were confirmed by consultation between all reviewers.

Ten studies (5 randomised and 5 non-randomised controlled trials), involving 770 participants, met the inclusion criteria for the review. Treatment regimes using opioid antagonists to induce withdrawal, with minimal sedation, varied in a number of aspects preventing description of a "standard" approach. Antagonist-induced withdrawal is associated with similar or less overall severity than withdrawal managed primarily with an alpha2 adrenergic agonist. This is probably because of earlier resolution of withdrawal. Peak severity is likely to be higher with antagonist-induced withdrawal and require the use of additional adjunct medications. Withdrawal from methadone may be more severe than withdrawal from heroin, but data are limited. Antagonist-induced withdrawal appears to be associated with somewhat higher rates of completion of withdrawal and achievement of maintenance doses of naltrexone but there were insufficient data for statistical analyses. The benefit of higher rates of completion of withdrawal is lessened by apparently low rates of retention in subsequent naltrexone maintenance treatment.

The use of opioid antagonists combined with alpha2 adrenergic agonists is feasible and probably increases the likelihood of transfer to naltrexone compared to 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.