Lofexidine for opiate detoxification: review of recent randomised and open controlled trials

The objective of this article was to review the data from recently published trials of lofexidine in the treatment of opiate withdrawal, with particular attention to evidence on efficacy, side-effects (particularly hypotension), and the acceptability of this new treatment to the patient population. The authors reviewed data contained within peer-reviewed published reports of clinical trials of lofexidine compared with detoxification using reducing doses of the opiate agonist methadone or the alpha-adrenergic agonist clonidine. Five published reports of clinical trials of lofexidine have been identified from peer-reviewed journals in the eight years between 1990 and 1998--all published within the last three years. Three of the reports compare lofexidine with clonidine, while the remaining two compare it with methadone detoxification. The three comparisons with clonidine find lofexidine to be similar in its moderating effect on the withdrawal syndrome, but without the same extent of problems with hypotension. Comparisons with methadone show a more rapid resolution of withdrawal symptoms with lofexidine--particularly with the accelerated 5-day lofexidine protocol. Such problems of hypotension as were encountered with lofexidine were adequately managed with dose reduction. Acceptability of the treatment to the patient (as measured by retention in treatment) appears to be greater with lofexidine than clonidine, although possibly less than with methadone. Lofexidine is an alpha-2 adrenergic agonist that is increasingly used in the management of opiate withdrawal--notably in the UK. The available data indicate that it is a useful new addition to the armamentarium of the clinician. Future studies should explore its application with improved protocols and in new treatment settings. This article reviews the recent advances in the study of lofexidine as a new treatment for opiate detoxification. It examines the background of the development and introduction of lofexidine into the U.K., with data on the extent to which it is now used in the U.K. in the treatment of opiate addiction. A review is then provided of the published evidence on the use of lofexidine in the management of opiate detoxification, mainly concentrating on the data from recent double-blind randomised trials. Finally, the possible future role of lofexidine in this field is considered.