Association between NMDAR antagonists, drug abuse and dependence: A disproportionality analysis from the WHO pharmacovigilance database.
British journal of clinical pharmacology November 1, 2022 Bruno Revol, Maryse Lapeyre-Mestre, Nathalie Fouilhé Sam-Lai et al.
All four N-methyl-D-aspartate receptor (NMDAR) antagonists examined—dextromethorphan, ketamine, amantadine, and memantine—showed a statistically significant association with reports of drug abuse and dependence in the World Health Organization pharmacovigilance database (VigiBase®), which contains over 21 million case reports from more than 130 countries. The strongest signal was for dextromethorphan, followed by ketamine, with weaker but still significant signals for amantadine and memantine. This suggests a possible class effect for abuse potential among NMDAR antagonists. The authors call for further investigation and alert health professionals to this risk, especially given growing interest in these drugs as non-opioid pain treatments during the opioid epidemic.