Key results:
We are uncertain whether peak withdrawal induced by opioid antagonists plus clonidine or lofexidine is more severe than withdrawal managed with clonidine or lofexidine alone, or whether the average severity over the withdrawal period is less, as the certainty of the evidence is very low.

Clinicians should warn people of the possibility of delirium in the first day of administration of naltrexone, particularly with higher doses (> 25 mg). People should also know that withdrawal will be moderately severe and that symptoms such as muscle aches, vomiting and diarrhoea, and insomnia are likely to persist despite medication.