Lofexidine in Combination With Oral Naltrexone for Opioid Use Disorder Relapse Prevention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND AND

OBJECTIVES

Lofexidine (LFX), an α2A adrenergic receptor agonist, known to alleviate opioid withdrawal symptoms, was assessed in combination with oral naltrexone (NTX) for effects on opioid use outcomes and NTX treatment compliance.

METHODS

Detoxified individuals (ages 18-55, 80% male) with opioid use disorder Diagnostic and Statistical Manual of Mental Disorders, 4th edition were randomized to 2.4 mg/day of LFX (n = 26) or Placebo (PBO, n = 31) in a double-blind manner for 12 weeks of treatment. NTX compliance, opioid-free urine samples, opioid craving as well as vital signs, subjective opioid withdrawal symptoms were assessed.

RESULTS

Intent to treat analysis revealed significantly better control over opioid craving in the LFX/NTX vs PBO/NTX group (P < .03), but no differences between groups in NTX compliance, opioid use, and overall opioid craving. However, subject withdrawal due to medication intolerance was significantly higher in the LFX/NTX (5/26) vs PBO/NTX (0/31) (P < .01). Two additional patients were withdrawn due to acute hepatitis infection. Post hoc secondary analyses with the nonwithdrawn sample indicated significantly higher rates of treatment completion (P < .05) and NTX compliance (P < .01), lower percent opioid urine samples (P < .05), and lower overall opioid craving (P < .05) in the LFX/NTX vs the PBO/NTX group.

CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Although preliminary, these findings suggest that LFX at doses up to 2.4 mg/daily was safe and improved control over opioid cravings. Among those who tolerated the medication, LFX/NTX significantly improved the opioid craving, delayed return to opioid use, and improved treatment compliance and completion rates. These findings support further assessment of LFX dose titration schedule along with the adjunctive use of LFX with NTX treatment to enhance opioid relapse prevention. (Am J Addict 2019;00:1-9).