Summary

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• This summary is based on the review of three systematic review(s)/meta-analysis(es). ^[1-3]
• Lofexidine and clonidine were found to be generally equivalent in mitigating opioid withdrawal symptoms, with four out of five studies showing no significant difference between the two, while one study reported lofexidine to be more effective in reducing withdrawal symptom severity.
• Lofexidine demonstrated no significant differences in detoxification completion rates compared to clonidine, but it was noted to have fewer adverse effects, with clonidine causing more frequent hypotension and feelings of unwellness.
• Lofexidine may play a role in stress management during opioid use disorder (OUD) treatment, particularly for individuals exposed to illicitly manufactured fentanyl (IMF), although its effectiveness as an adjunctive medication in such settings remains supported by limited evidence.
• In one study, lofexidine led to significant hypotension, bradycardia, and pupillary constriction compared to a placebo.
• Despite these adverse effects, lofexidine demonstrated a better safety profile overall when compared to clonidine in managing opioid withdrawal symptoms.
• The reviewed studies primarily focused on adults with OUD, including those with exposure to IMF, which complicates opioid withdrawal management. Stress management, particularly in individuals undergoing medication-assisted treatment (MAT) for OUD, was a key focus, with both lofexidine and clonidine showing potential benefits. Lofexidine's role in stress reduction and adjunctive use in IMF-exposed populations, alongside shorter induction protocols for quicker treatment initiation, was highlighted as potentially improving outcomes in high-risk groups.