Memantine improves buprenorphine/naloxone treatment for opioid dependent young adults

Abstract

Background: Opioid use disorders are considered a serious public health problem among young adults. Current treatment is limited to long-term opioid substitution therapy, with high relapse rates after discontinuation. This study evaluated the co-administration of memantine to brief buprenorphine pharmacotherapy as a treatment alternative.

Methods: 13-week double-blind placebo-controlled trial evaluating 80 young adult opioid dependent participants treated with buprenorphine/naloxone 16-4mg/day and randomized to memantine (15mg or 30mg) or placebo. Primary outcomes were a change in the weekly mean proportion of opioid use, and cumulative abstinence rates after rapid buprenorphine discontinuation on week 9.

Results: Treatment retention was not significantly different between groups. The memantine 30mg group was significantly less likely to relapse and to use opioids after buprenorphine discontinuation. Among participants abstinent on week 8, those in the memantine 30mg group (81.9%) were significantly less likely to relapse after buprenorphine was discontinued compared to the placebo group (30%) (p<0.025). Also, the memantine 30mg group had significantly reduced opioid use (mean=0, SEM±0.00) compared to the placebo group (mean=0.33, SEM±0.35; p<0.004) during the last 2 weeks of study participation.

Conclusions: Memantine 30mg significantly improved short-term treatment with buprenorphine/naloxone for opioid dependent young adults by reducing relapse and opioid use after buprenorphine discontinuation. Combined short-term treatment with buprenorphine/naloxone may be an effective alternative treatment to long-term methadone or buprenorphine maintenance in young adults.

Keywords: Buprenorphine; Early relapse; Memantine; Opioid dependence; Young adults.

Fig. 1

Consort diagram summarizing participant flow.

Fig. 2

Change of weekly opioid use by treatment groups. Weekly mean proportion of opioid use by treatment groups during 13 weeks. Each data point is mean ± SEM and * signifies a significant difference between the groups during that week (p < 0.05). Participants were inducted, stabilized and then discontinued on buprenorphine as marked on bottom of figure. The arrow indicates the week buprenorphine was discontinued.

Fig. 3

Fitted probability of opioid use per week by treatment group. A. Overall effect (weeks 1 to 13). B. After buprenorphine induction (weeks 2 to 13). C. Before buprenorphine discontinuation (weeks 2 to 8) and D. After buprenorphine discontinuation (week 8 to 13). Calculated from mixed-effect regression analyses models that controlled for baseline mean proportion of weekly opioid use with COWS, ASI psychiatric, and legal composite scores as covariates.

Fig. 4

Cumulative proportion remaining abstinent after buprenorphine discontinuation. The data point represents the cumulative proportion from week 8 that remained abstinent, after achieving abstinence on week 8. The arrow represents the week buprenorphine was discontinued.