Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial

Abstract

Objectives:To investigate the safety and efficacy of lofexidine for treating opioid withdrawal syndrome (OWS) and facilitating completion of opioid withdrawal.Methods:A multicenter, double-blind, placebo-controlled study was conducted at 18 US centers from June 2013 to December 2014. Participants (n=603) aged ≥18 years, dependent on short-acting opioids, and seeking withdrawal treatment, randomized 3:3:2 to receive lofexidine 2.88mg/d (n=222), lofexidine 2.16mg/d (n=230), or placebo (n=151) for 7 days. Primary outcome was the Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) scores rating withdrawal symptoms over days 1 to 7.Results:Participants were of mean age, 35 years; 71% male. Pairwise differences in overall SOWS-Gossop log-transformed least squares means were statistically significant for lofexidine 2.16mg (difference, -0.21; 95% CI, -0.37 to -0.04; P=0.02) and 2.88mg (-0.26; 95% CI, -0.44 to -0.09; P=0.003) compared with placebo. Fewer than half of participants in both groups completed the study. Completion rates for lofexidine 2.16mg (41.5%; odds ratio [OR], 1.85; P=0.007) and 2.88mg (39.6%; OR, 1.71; P=0.02) were significantly better compared with placebo (27.8%). Overall adverse event (AE) rates were similar across groups. Common AEs for lofexidine included orthostatic hypotension, hypotension, and bradycardia, but resulted in few study discontinuations.Conclusions:Lofexidine 2.16mg and 2.88mg significantly reduced symptoms of OWS versus placebo, and increased absolute rates of completing the 7-day study by 14% and 12%, respectively (a relative increase of 85% and 71%). Data suggest that lofexidine is a generally safe and effective nonopioid treatment for opioid withdrawal. Lofexidine could serve as a withdrawal treatment option when a nonopioid agent is preferred or required, when agonist-assisted withdrawal is unavailable, when agonist discontinuation caused OWS, and during induction into maintenance treatment with opioid agonists or antagonists.Trial Registration:ClinicalTrials.gov identifier: NCT01863186.