Adjunctive memantine for opioid use disorder treatment: A systematic review

Memantine is commonly used for the treatment of moderate-to-severe Alzheimer's disease. Due to its antagonism of the N-methyl-d-aspartate (NMDA) receptor, which has been shown to block rewarding and reinforcing effects of morphine, memantine has been investigated for potential utilization in opioid use disorder (OUD). The objective of this systematic review is to assess the evidence available to determine the safety and efficacy of memantine as treatment for OUD. Pubmed (1946-August 2019) and Embase (1947-August 2019) were queried using the following search terms: opioid-related disorders, opioids, substance withdrawal syndrome, withdrawal syndrome, opiate addiction, opiate, opiate dependence, opiate substitution treatment, managed opioid withdrawal, or drug withdrawal and memantine. After assessing studies appropriate for the objective, one single-blind and five double-blind, placebo-controlled trials were included. Of the included studies, four demonstrated beneficial effects of memantine either as monotherapy or adjunct to methadone or buprenorphine on reducing opioid cravings and methadone dose, increasing retention rates, and improving cognitive performance in patients with OUD. Two studies did not show benefit on patient retention rates with memantine adjunct to naltrexone. Study durations ranged from 3 to 13 weeks, and memantine dosing ranged from 5 to 60 mg/day. Memantine was well tolerated with similar rates of adverse effects between treatment groups. Based on the reviewed literature, memantine appears most beneficial as an adjunctive treatment for OUD when combined with methadone or buprenorphine, but not naltrexone. Larger studies with longer periods of treatment and follow-up are needed to support the use of memantine in the management of OUD.