A placebo-controlled trial of memantine as an adjunct to injectable extended-release naltrexone for opioid dependence

There is preclinical support for using NMDA receptor glutamatergic antagonists to aid in naltrexone-based treatment of opioid dependence. We hypothesized that adding memantine will improve efficacy of extended-release (XR) naltrexone to prevent relapse. In this double blind study opioid-dependent participants (N = 82) underwent inpatient detoxification and naltrexone induction. During naltrexone initiation participants were randomized to receive memantine 40 mg or placebo and continued treatment for 12-weeks with XR naltrexone and relapse-prevention therapy. Sixty eight percent of participants completed detoxification and received the first dose of XR naltrexone. Rates of trial completion were significantly greater in participants receiving placebo than memantine (70% vs. 43%, p < 0.05). Severity of opioid withdrawal symptoms during the first 3 weeks of the trial appeared to be lower in the group receiving memantine (p = 0.07). Adding memantine does not appear to increase the effectiveness of injectable XR naltrexone as a relapse prevention strategy in opioid dependence and may lead to an increase in treatment drop-out.