Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal

Drug Alcohol Depend. 1997 Nov 25;48(2):127-33. doi: 10.1016/s0376-8716(97)00116-6.


Lofexidine is an analogue of clonidine, an agonist at the alpha 2 noradrenergic receptor. Reports from preliminary open studies have suggested that it may be at least as effective as clonidine in the management of opiate withdrawal, and without the same limitation of postural hypotension. We report on a randomised double-blind comparison of lofexidine versus clonidine in the treatment of heroin withdrawal. A total of 80 hospitalized heroin addicts were randomly assigned to treatment with lofexidine or clonidine during in-patient opiate withdrawal. Maximum daily doses were 1.6 mg for lofexidine and 0.6 mg for clonidine. There was marked diurnal variation of withdrawal symptoms with severity being greatest at the daytime reading at 16.00 h and being markedly less at the night-time reading (recorded at 08.00 h). Lofexidine and clonidine were equally effective in treating the withdrawal syndrome. However, significantly more problems relating to hypotension were encountered with subjects on clonidine, with twice as many instances of withholding medication due to hypotension in the clonidine group. Better treatment retention rates were seen in the lofexidine group, although no difference was found in the proportion who had reached minimal symptom severity by the time of their discharge. We conclude that lofexidine and clonidine are equally effective, but with significantly fewer hypotensive problems with lofexidine. Further benefit from lofexidine may be possible with revised dosing regimens. Outpatient studies of lofexidine are now indicated.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Circadian Rhythm
  • Clonidine / administration & dosage
  • Clonidine / adverse effects*
  • Clonidine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Heroin*
  • Humans
  • Hypotension, Orthostatic / chemically induced
  • Male
  • Narcotic Antagonists / administration & dosage
  • Narcotic Antagonists / adverse effects*
  • Severity of Illness Index
  • Substance Withdrawal Syndrome / diagnosis
  • Substance Withdrawal Syndrome / drug therapy*


  • Narcotic Antagonists
  • Heroin
  • Clonidine
  • lofexidine