Randomized, placebo-controlled trial of gabapentin during outpatient buprenorphine-assisted taper and transition to injectable naltrexone

<i>Background:</i> Gabapentin may help manage opioid withdrawal symptoms, but its effectiveness during buprenorphine taper and transition to naltrexone is uncertain.<i>Objectives:</i> To assess gabapentin's efficacy in improving outcomes for lifetime prescription opioid use disorder (POUD) during outpatient buprenorphine taper and transition to extended-release naltrexone.<i>Methods:</i> This 12-week randomized, double-blind, placebo-controlled trial enrolled 117 (55% male) POUD participants. Weeks 1-3, participants attended clinic 5 days/week for medication, therapy, and assessments, including weekly craving and thrice-weekly opioid withdrawal and supervised urine screens. Participants were inducted onto buprenorphine (12 mg), randomized to receive either placebo or gabapentin (800 mg BID), and underwent a 10-day buprenorphine taper. In week 4, participants transitioned from oral to extended-release naltrexone. Chi-square and generalized estimating equation models assessed outcomes. A subset with baseline fentanyl tests was also examined for fentanyl's impact on outcomes.<i>Results:</i> Of 117 participants, 75 (64.1%) completed the buprenorphine taper (41 gabapentin, 34 placebo), and 24 (20.5%) transitioned to naltrexone (12 gabapentin, 12 placebo). No significant group differences were observed in taper completion, naltrexone transition, craving, withdrawal, or opioid use. Fentanyl-positive participants had lower taper completion (47.8% vs. 75.8%, OR = 0.286, <i>p</i> = .033) and more opioid-positive urines (z = -4.24, <i>p</i> < .0001). Fentanyl-positive participants on gabapentin had higher COWS (z = 3.70, <i>p</i> = .001) and SOWS (z = 3.73, <i>p</i> = .001) scores, while fentanyl-negative participants on gabapentin had lower SOWS scores than those on placebo (z = -3.52, <i>p</i> = .002).<i>Conclusions:</i> Fentanyl exposure impairs buprenorphine taper success and worsens withdrawal in the presence of gabapentin, underscoring the need to tailor OUD treatment in fentanyl-exposed patients. (Clinicialtrials.gov ID NCT02543944).