Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore

J Subst Abuse Treat. 2018 Aug:91:1-11. doi: 10.1016/j.jsat.2018.04.012. Epub 2018 Apr 25.

Abstract

Background: Many individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications.

Design and procedures: The study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving.

Main findings: The OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification.

Conclusions: Lofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.

Trial registration: ClinicalTrials.gov NCT01675648.

Keywords: Diazepam; Inpatients; Lofexidine; Opioid-withdrawal syndrome; Placebo-controlled; RCT.

Publication types

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

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / administration & dosage
  • Adrenergic alpha-2 Receptor Agonists / adverse effects
  • Adult
  • Clonidine / administration & dosage
  • Clonidine / adverse effects
  • Clonidine / analogs & derivatives*
  • Craving / drug effects
  • Diazepam / administration & dosage*
  • Diazepam / adverse effects
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / adverse effects
  • Male
  • Middle Aged
  • Opioid-Related Disorders / drug therapy*
  • Pupil / drug effects
  • Singapore
  • Substance Withdrawal Syndrome / drug therapy*

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Hypnotics and Sedatives
  • Clonidine
  • Diazepam
  • lofexidine

Associated data

  • ClinicalTrials.gov/NCT01675648