Lofexidine versus clonidine for mitigation of opioid withdrawal symptoms: A systematic review

Kuszmaul, Amanda K.; Palmer, Emma C.; Frederick, Emily K.

Objectives: The U.S. Food and Drug Administration recently approved lofexidine, an alpha-2-adrenergic agonist, as the first non-opioid medication for mitigation of opioid withdrawal symptoms. Clonidine, an alpha-2-adrenergic agonist, historically was used off-label for this indication. This review aimed to evaluate the effectiveness of lofexidine versus clonidine for mitigation of opioid withdrawal symptoms and to discuss the current role of lofexidine in the management of patients at risk of experiencing opioid withdrawal. Data sources: MEDLINE/PubMed, EBSCO, and CENTRAL were searched using the terms "lofexidine," "clonidine," and "opioid withdrawal." Study selection: The literature search included English-language studies involving administration and prescription of lofexidine and clonidine for the management of opioid withdrawal symptoms in adults. Data sources were searched to include articles published between October 1993 and May 2019. Data extraction: Three independent reviewers analyzed the title and abstract of studies to identify studies involving comparisons of lofexidine with clonidine for mitigation of opioid withdrawal symptoms. Reviewers were initially blinded to the individual determinations. Results were then unblinded and discussed among reviewers. Results: Of the 110 citations screened, 5 articles were included. One study demonstrated a statistically significant reduction in opioid withdrawal symptom severity with lofexidine compared with clonidine, whereas the other 4 studies showed no significant difference. Three studies reported the completion of opioid detoxification treatment, with no significant differences seen. In 1 study that compared lofexidine with placebo, lofexidine caused significant hypotension, bradycardia, and pupillary constriction. Three studies showed significant adverse effects of hypotension and symptoms of feeling unwell with clonidine compared with lofexidine. Conclusion: Lofexidine appears equivalent in efficacy to clonidine, with fewer adverse effects, and it may have a limited role in the management of opioid withdrawal symptoms. However, cost, detoxification venue, and value of other preferred treatment modalities may affect the comparative efficacy of lofexidine to other agents. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.