TY - JOUR
T1 - Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal
T2 - A Randomized Controlled Clinical Trial
AU - Fishman, Marc
AU - Tirado, Carlos
AU - Alam, Danesh
AU - Gullo, Kristen
AU - Clinch, Thomas
AU - Gorodetzky, Charles W.
N1 - Funding Information:
Additional contributions: Editorial support was provided by The Curry Rock-efeller Group, LLC, and was funded by US WorldMeds.
Funding Information:
Conflicts of interest: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Fishman is a consultant for US WorldMeds, LLC, and for Alkermes, and reported receiving study funding from NIDA, Arnold Foundation, and Media Rez. Dr Tirado reported serving on speaker panels for Indivior and Alkermes plc. Dr Alam is a consultant for US WorldMeds, LLC, and for Alkermes, and reported receiving research support from Allergan, Otsuka, Janssen, and Alkermes. Ms Gullo is an employee and shareholder of US World-Meds, LLC. Mr Clinch is an employee and shareholder of US WorldMeds, LLC. Dr Gorodetzky is a consultant to US WorldMeds, LLC. This work was supported by US WorldMeds, LLC, and the National Institute on Drug Abuse (grant U01DA033276).
Funding Information:
This work was supported by USWorldMeds, LLC, and the National Institute on Drug Abuse (grant U01DA033276).
Publisher Copyright:
© 2018 American Society of Addiction Medicine.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - lofexidine
KW - opioid use disorder
KW - opioid withdrawal
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U2 - 10.1097/ADM.0000000000000474
DO - 10.1097/ADM.0000000000000474
M3 - Article
C2 - 30531234
AN - SCOPUS:85061590306
SN - 1932-0620
VL - 13
SP - 169
EP - 176
JO - Journal of addiction medicine
JF - Journal of addiction medicine
IS - 3
ER -