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

Background

Gabapentin may help manage opioid withdrawal symptoms, but its effectiveness during buprenorphine taper and transition to naltrexone is uncertain.

Objectives

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.

Methods

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.

Results

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, p = .033) and more opioid-positive urines (z = -4.24, p < .0001). Fentanyl-positive participants on gabapentin had higher COWS (z = 3.70, p = .001) and SOWS (z = 3.73, p = .001) scores, while fentanyl-negative participants on gabapentin had lower SOWS scores than those on placebo (z = -3.52, p = .002).

Conclusions

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).